Renal and vesical calculi
Approximately 2% of the population in the UK have a urinary tract stone at any given time. A much higher prevalence of stone disease has been recorded elsewhere, notably in the Middle East. In the Western World, most stones occur in the upper urinary tract. The incidence of bladder stones has declined in the UK since the eighteenth and nineteenth centuries, whereas in some developing countries they are still common. Most stones are composed of calcium oxalate and phosphate; these are commoner in men.
Mixed infective stones, which account for about 20% of all calculi, are twice as common in women as in men. The overall male/female ratio of stone disease is 2 : l. Stone disease is frequently a recurrent problem. More than 50% of patients with a calculus will have formed a further stone or stones within 10 years. The risk of recurrence increases if a metabolic or other abnormality predisposing to stone formation is present and is not modified by treatment.
It is in a sense surprising that stones are not universal, since some constituents of urine are at times present in concentrations that exceed their maximum solubility in water. The presence of inhibitors of crystal formation in normal urine appears to be of importance in preventing stones.
Many stone-formers have no detectable metabolic defect, although microscopy of warm, freshly passed urine reveals both more and larger calcium oxalate crystals than are found in normal subjects. Factors predisposing to stone formation in these so-called ‘idiopathic stone-formers’ are:
CHEMICAL COMPOSITION OF URINE that favours stone crystallization
PRODUCTION OF A CONCENTRATED URINE as a consequence of dehydration associated with life in a hot climate or work in a hot environment
IMPAIRMENT OF INHIBITORS that prevent crystallization in normal urine. Recognized causes of stone formation are listed.
If the GFR is normal, hypercalcaemia almost invariably leads to hypercalciuria. The common causes of hypercalcaemia leading to stone formation are:
• Primary hyperparathyroidism
• Vitamin D ingestion
Of these, primary hyperparathyroidism is the commonest cause of stones.
This is by far the commonest metabolic abnormality detected in calcium stone-formers. Approximately 8% of men excrete in excess of 7.5 mmol calcium per 24 hours. Calcium stone formation is commoner in this group, but as most patients do not form stones the definition of ‘pathological’ hypercalciuria is arbitrary. A reasonable definition of pathological hypercalciuria is excretion of more than 7.5 mmol calcium per 24 hours in male and more than 6.25 mmol calcium per 24 hours in female stone-formers.
Causes of hypercalciuria are:
• An excessive dietary intake of calcium
• Excessive resorption of calcium from the skeleton, such as occurs with prolonged immobilization or weightlessness
• Idiopathic hypercalciuria
The majority of patients with idiopathic hypercalciuria can be shown to have increased absorption of calcium from the gut. Dietary calcium restriction in this group markedly reduces urinary calcium excretion. However, a proportion of these patients appear to have a renal tubular calcium leak with secondary compensatory hyperabsorption of calcium from the gut. Calcium restriction has less effect on urinary calcium excretion in this group.
Two inborn errors of glyoxalate metabolism that cause increased endogenous oxalate biosynthesis are known. Both are inherited in an autosomal recessive manner. In type I (primary hyperoxaluria) there is increased glycolate excretion as well as hyperoxaluria. In type II L-glycerate excretion is increased. In both types, calcium oxalate stone formation occurs.
The prognosis is poor owing to widespread calcium oxalate crystal deposition in the kidneys. Renal failure typically develops in the late teens or early twenties. Much commoner causes of mild hyperoxaluria are:
EXCESS INGESTION OF HIGH OXALATE-CONTAINING FOOD, such as spinach, rhubarb and tea.
DIETARY CALCIUM RESTRICTION, with compensatory increased absorption of oxalate.
GASTROINTESTINAL DISEASE, such as Crohn’s disease, usually with an intestinal resection is associated with increased absorption of oxalate from the colon. Dehydration secondary to fluid loss from the gut also plays a part in stone formation.
Hyperuricaemia and hyperuricosuria
Uric acid stones account for 3-5% of all stones in the UK, but in Israel the proportion is as high as 40%. Uric acid is the end-point of purine metabolism. Hyperuricaemia can occur as a primary defect in idiopathic gout, and as a secondary consequence of increased cell turnover, e.g. in myeloproliferative disorders. Increased uric acid excretion occurs in these conditions, and stones will develop in some patients. Some uric acid stone-formers have hyperuricosuria (>4 mmol/24 hours on a low purine diet) without hyperuricaemia. Dehydration alone may also cause uric acid stones to form. Patients with ileostomies are at particular risk both from dehydration and from the fact that loss of bicarb onate from gastrointestinal secretions results in the pro- (a) duction of an acid urine (uric acid is more soluble in an alkaline than an acid medium).
Some patients with calcium stones also have hyperuricaemia and/or hyperuricaciduria; it is believed the calcium salts precipitate upon an initial nidus of uric acid in such patients.
Mixed infective stones are composed of magnesiumammonium phosphate together with variable amounts of calcium. Such stones are often large, forming a cast of the collecting system (staghorn calculus). They are believed to form as a result of infection of the urinary tract with organisms such as Proteus mirabilis that hydrolyse urea, with formation of the strong base ammonium hydroxide.
The availability of ammonium ions and the alkalinity of the urine favour stone formation. An increased amount of mucoprotein resulting from infection also creates an organic matrix on which stone formation can occur.
Cystinuria results in the formation of cystine stones. About 1-2% of all stones are composed of cystine.
Primary renal diseases
There is a moderate increase in prevalence of stone disease in patients with polycystic renal disease.
Medullary sponge kidney is another primary renal disorder associated with stones. In this congenital (though not inherited) condition there is dilatation of the collecting ducts with associated stasis and calcification. Approximately 20% of these patients have hypercalciuria and a similar proportion have a renal tubular acidification defect.
The renal tubular acidoses, both inherited and acquired, are associated with nephrocalcinosis and stone formation owing, in part at least, to the production of a persistently alkaline urine and reduced urinary citrate excretion.
Aetiology of bladder stones
Bladder stones are endemic in some developing countries.The cause of this is unknown but dietary factors are probably important. Stones forming in the bladder do so as a result of:
BLADDER OUTFLOW OBSTRUCTION, e.g. urethral stricture, neuropathic bladder, prostatic obstruction
THE PRESENCE OF A FOREIGN BODY, e.g. catheters, non-absorbable sutures. Significant bacteriuria is usually found in patients with bladder stones. Some stones found in the bladder have
been passed down from the upper urinary tract.
Stones may be single or multiple and vary enormously in size from sand-like minute particles to staghorn calculi or large stone concretions in the bladder. They may be located within the renal parenchyma or within the colleering system. Pressure necrosis from a large calculus may cause direct damage to the renal parenchyma and stones regularly cause obstruction, leading to hydronephrosis. They may ulcerate through the wall of the collecting system, including the ureter. A combination of obstruction and infection accelerates damage to the kidney.