Section 1 Epidemiology and aetiology
The lifetime prevalence for renal stones is 1-15 per cent. Peak incidence is at 35 and 55 years for females and 30 years for males. There is seasonal variation for calcium oxalate stones: summer for males and winter for females.
Dehydration plays a main role in urinary stone formation. Daily fluid intake of less than one litre increases urinary calcium secretion in 20-40 per cent of patients, urine oxalate in 40 per cent of male and 10 per cent of female patients and promotes hyperuricosuria.
Stone formation starts when dissolved urinary salts become solid (supersaturation).
This is driven by an imbalance between promoters (calcium oxalate, calcium phosphate, uric acid, magnesium ammonium phosphate and cystine) and inhibitors (pyrophosphates, glycoproteins, nephrocalcin, Tamm-Horsfall protein, citrate, magnesium, glycosaminoglycons, osteopontin, lithostatin, bikunin). Urinary pH plays a key role.
Calcium is the main component of most of renal stones (calcium oxalate, calcium phosphate). Hypercalciuria is a result of intestinal hyper-absorption (absorptive hyper-calciuria), impaired renal tubular reabsorption (renal hypercalciuria, secondary parathyroidism) and primary hyperparathyroidism (resorptive hypercalciuria).
Idiopathic calcium oxalate is the most common urinary stone. Hyperoxaluria can be a result of increased intestinal absorption due to bowel disorders as well as low calcium intake (enteric hyperoxaluria). Vitamin C overdose and abnormal oxalate biosynthesis (primary hyperoxaluria) also contribute to hyperoxaluria.
Low urinary pH (<5.5) promotes the undissociated form of uric acid (monosodium urate). The process may initiate uric acid as well as calcium oxalate stone formation. A urinary pH >5.5 uric acid induces calcium oxalate only (hyperuricosuria occurs in 10 per cent patients with calcium stones).
Conditions leading to chronic metabolic acidosis decrease urinary pH and cause hypercalciuria and hypocitraturia. The main source of urinary uric acid is dietary purine intake.
Gout, myeloand lymphoproliferative disorders, multiple myeloma, haemolytic disorders, pernicious anaemia, hemoglobinopathies and hereditary renal hypouricemia also increase urinary uric acid.
Epidemiological studies show that urinary stone formers present as overweight (89 per cent), with hypercholesterolemia (43.5 per cent), hypertention (31.5 per cent), diabetes mellitus (3.5 per cent) and physical inactivity (14 per cent).1 Gout increases the risk of uricosuria.
Patients with a BMI >25 kg/m2 excrete more uric acid, phosphate, ammonium in urine and have low urinary pH.
A cohort study showed 59.2 per cent of males and 43.9 per cent of females with idiopatic calcium oxalate renal stones were overweight.2
Intensive intake of salt is responsible for hypertension as well as urinary stone formation. A study showed that 21 per cent of diabetic patients had urinary stones compared with 8 per cent for non-diabetic patients.3
Insulin resistant diabetes impairs renal ammonium production and urinary citrate excretion, which results in decreased urinary pH.
Drugs are responsible for 1-2 per cent of renal stones as their metabolites can be components or induce formation by interfering with calcium oxalate or purine metabolism.4
UTIs may result in struvite and carbonate apatite stones. Splitting urea into ammonia and carbon dioxidate results in increased urinary pH, decreased magnesium and calcium solubility.
Ammonia in the urine and urinary pH >7.2 are required for struvite stone formation.
Section 2 Presentation and investigations
Patients with anatomical abnormalities of the upper urinary tract resulting in obstructed urine drainage are at significant risk.
This includes: ureteropelvic junction obstruction, ureteric stricture, renal diverticulae, horseshoe kidney, ureterocele, vesicoureteric reflux, medullary sponge kidney.
Some genetically determined conditions predispose to urolithiasis, such as cystinuria, primary hyperoxaluria, renal tubular acidosis, adenine phosphoribosyltransferase deficiency, and xanthinuria.
Small renal stones causing no obstruction are almost always asymptomatic (one third may become symptomatic). Patients present with different symptoms at different ages (click here to see different symptom stages).
Children are seen often with UTIs, some abdominal pain or haematuria, rather than typical renal colic. Blockage to the renal collecting system causes its distension. Therefore pain is initially localised to the loin.
Further loin pain starts radiating to the groin and has a typical colicky character. As the ureter crosses the genito-femoral nerve, ureteric dilatation or inflammation may compress the nerve inducing pain radiation to the groin. Closer to the bladder the stone may cause urinary frequency and urgency. Pain lasting less than 12 hours is characteristic for renal colic.
Trauma and haematuria
The stone may cause trauma to the upper urinary tract on its journey and cause haematuria in 95-100 per cent of patients. Renal stone patients can also present with nausea, vomiting (the same nerves innervate the renal capsule and bowel), fever and chills.
An ultrasound scan together with kidney, ureter and bladder X-rays (KUB) still remain the primary investigations for renal colic, but they do not provide enough information and further tests are usually required.
The Royal College of Radiologists list both as indicated only in specific circumstances.
However, KUB or ultrasound can be used for assessment of stone clearance after fragmentation.
Non-contrast helical CT is the best investigation for diagnosis of loin pain suggesting renal colic, with a sensitivity of up to 100 per cent and specificity up to 98 per cent. Its introduction increased the detection rate of non-urinary lesions from 16 per cent to 45 per cent.
Section 3 Prophylaxis
First-time stone formers require a blood test for creatinine, calcium and uric acid.
The risk of them getting a new stone is only 30 per cent. Almost 70 per cent of recurrent stone formers require follow-up and metabolic evaluation as approximately 25 per cent may be diagnosed with one of: hypercalciuria, hyperuricosuria, hypocitraturia, renal tubular acidosis, hyperoxaluria.5
Dietary and pharmacological manipulations can reduce recurrence rate by 22.6 per cent.6
Increasing fluid intake prevents urinary stones formation. Fluid intake of three litres is recommended as it keeps daily urine volumes above 2.5 litres.
Cystine stones require forced diuresis with fluid intake >four litres a day. Although filtered water is recommended, carbonated water is believed to increase urinary citrate (rich in bicarbonate).
Up to 60 per cent of calcium stone formers present with hypocitraturia. Citrate builds soluble complexes with calcium and reduces saturation of calcium oxalate as well as calcium phosphate stones.
As potassium citrate (Kcit) is involved in alkali load as well as renal handling of citrate, it is recommended for stone prevention. Treatment with Kcit is expensive and poorly tolerated by patients.
Fruits and vegetables rich in potassium increase urinary citrate. Such a diet can also increase magnesuria. Absorbed citrate is mostly metabolised in the liver to bicarbonate, causing an increase in intracellular pH.
A diet rich in fruit and vegetables reduces relative saturation for calcium oxalate and uric acid in hypocitraturic stone formers.
Cranberry juice is not recommended for prophylaxis as it does not affect urinary citrate and can increase urinary saturation of calcium oxalate. It increases urinary magnesium with no prophylactic result.
Decreasing urinary pH is the only benefit of cranberry juice, as it reduces urinary saturation of calcium phosphate. The juice reduces serum and urine uric acid, but it does increase concentration of insoluble uric acid at the same time.
Orange juice (high in potassium and citrate) increases urinary citrate in hypocitraturic stone formers.
High salt intake results in high calcium excretion (increased calcium turnover, potassium depletion and hypocitraturia).
Dietary calcium restrictions are not recommended as may result in secondary hyperoxaluria (except for absorptive hypercalciuria). A transient increase in urinary oxalate excretion following a diet containing oxalates has been observed. Therefore a restriction on foods containing large amounts of oxalate is advised.
However, epidemiological studies did not demonstrate any difference in oxalate intake between oxalate stone formers and non-formers.
Diet rich in animal protein results in low urinary pH, hypocitraturia and decreased calcium reabsorpition.
Control over pH plays a key role in uric acid stone prophylaxis as well as treatment. Patients are also advised restriction in food rich in purines, such as liver and kidney.
|DRUGS USED FOR PROPHYLAXIS|
|Thiazides||Correction of calcium renal leak||Does not help hyperabsorptive|
hypercalciuria, hypokalemia, muscle
|Sodium cellulose phosphate||Calcium binding to inhibit absorption|
|Expensive, GI side-effects,|
hypomagnesemia, parathyroid hormone
|Vitamin B6||Reduced hyperoxaluria, improved|
convertion of glyoxylate to glycine
|Magnesium||Binding oxalate in bowels, inhibition|
of calcium phosphate growth
|Diarrhoea, contraindicated for utis and|
may build struvite stones
|Allopurinol||Reduced uric acid synthesis, inhibition|
of xanthine oxidase
|Incresed cystine solubility||Nephrotic syndrome, dermatitis, |
Section 4 Medical management
Upper urinary tract stones can be passed. Spontaneous expulsion for stones <4 mm, <6mm and 5-11mm occurs in 80 per cent, 68 per cent and 47 per cent respectively.
The average chance of passing a ureteric stone is 25 per cent for proximal, 45 per cent for middle and 70 per cent for distal ureter. 95 per cent of stones <6 mm do not need a urologist's help to get into the bladder, but this may take time (up to 31 days for stones <3mm and up to 40 days for 6mm stones).
Most patients present with pain. Diclofenac is recommended as the first-line treatment.
Studies confirmed a high density of alpha-1 adrenergic receptors in the distal ureter.7 Therefore, starting an alpha-blocker improves stone expulsion rate, expulsion time and reduces the need for analgesia. Bothtamsulosin and alfuzosin have proven equally effective.8
Fever and difficult-to-control pain require urgent insertion of a stent or nephrostomy.
Treatment recommendations are as follows:
- Fluid intake (as well as citrus juices) should be encouraged.
- Salt and animal protein should be limited.
- Treatment for gout should be monitored.
- An active lifestyle should be promoted for BMIs of 18-25 kg/m2.
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2. Sienner R, Glatz S, Nicolay C et al. The role of overweight and obesity in calcium oxalate stone formation. Obes Res 2004; 12(1): 106-13.
3. Meydan N, Barutca S, Caliskan S. Urinary stone disease in diabetes mellitus. Scand J Urol Nephrol 2003; 37: 64-70.
4. Daundon M, Jungers P. Drug-induced renal calculi. Drugs 2004; 64 (3): 245-75.
5. Masood J. Long-term follow up of recurrent stone formers: who, how long and how often? BJU Int 2009; 105: 1-2.
6. Pearle M, Roehborn CG, Pak CY. Meta-analysis of randomised trials for medical prevention of calcium oxalate lithiasis. J Endourol 1999; 13: 679-85.
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8. Agrawal M, Gupta M, Gupta A et al. Prospective randomized trial comparing efficacy of alfuzosin and tamsulosin in management of lower ureteral stones. Urology 2009; 73: 706-9.