Struvite stones

Infective stones are frequently diagnosed in male children under 5 years of age, over 90% of whom have infected urine at the time of diagnosis.2 Stone fragments are soft and easily passed in the urine, and are sometimes described by parents as a paste. The urine infection may be resistant to antibiotic treatment and a proteus infection should always alert the physician to the possibility of renal calculi. The stone is frequently located in the upper tract, usually renal pelvis, and is termed “staghorn” as a result of its shape.

Calcium stones

Calcium containing stones are often associated with underlying metabolic abnormalities, particularly if nephrocalcinosis is also present (see table 2). In childhood, the three most common causes of nephrocalcinosis are hypercalciuric states, distal renal tubular acidosis, and the hyperoxalurias. Idiopathic hypercalciuria is not well understood, but two forms are described:

• Absorptive hypercalciuria, in which there is increased intestinal absorption of calcium

• Renal hypercalciuria, in which there is reduced renal tubular calcium reabsorption as a primary abnormality.

These two forms can be differentiated by the response to a low calcium diet as well as to calcium loading.6 ,7 The distinction between these two forms may be considered relevant as the absorptive hypercalciuria can be controlled by moderate dietary calcium restriction, whereas the renal hypercalciuria is managed by a thiazide diuretic. The introduction of a high potassium but low sodium diet is of benefit to hypercalciuric children as the urinary calcium excretion can be reduced, as long as the diet can be maintained.8 ,9Hyperparathyroidism is very rare in children and occasionally may cause renal calculi.

Frusemide use in low birth weight infants and cardiac patients is more frequently recognised nowadays as a cause of diffuse nephrocalcinosis. Frusemide inhibits the Na/K/2Cl channel in the thick ascending limb of the loop of Henle, which induces notable calciuria associated with the natriuresis.10 Nephrocalcinosis as a complication of the treatment of hypophosphataemic rickets, is much less frequently seen now, as a result of the use of 1,25-dihydroxycholecalciferol. It is suggested that this form of nephrocalcinosis is compounded by the hypercalciuria complicating oral phosphate supplementation.11

In distal renal tubular acidosis the finding of an alkaline urine and hypercalciuria with a low urinary citrate excretion, favours the precipitation of calcium salts with resultant stone formation. Therapy consists of sufficient alkali to neutralise endogenous acid production, but unfortunately stone formation sometimes continues despite adequate alkali supplementation.

Dent's disease is a renal tubular disorder characterised by low molecular weight proteinuria and hypercalciuria with nephrolithiasis, and is associated with inactivating mutations of the X linked chloride channel, CLC-5.12 ,13 The renal impairment is slowly progressive and rarely seen in childhood, although the other clinical features may be overlooked. An increase in the urinary excretion of low molecular weight proteins, beta 2-microglobulin, or retinol binding protein, is highly specific for renal tubular disease.14

Familial renal magnesium wasting, hypercalciuria with nephrocalcinosis, and partial distal renal tubular acidosis has been identified as a course of renal failure in children.15-17

Oxalate stones

The primary hyperoxalurias (PH) are rare autosomal recessive defects of oxalate metabolism that cause excessive endogenous oxalate production. The toxicity of oxalate in humans results from the extreme insolubility of its calcium salt, calcium oxalate, which may precipitate in the renal parenchyma or renal tract, causing either nephrocalcinosis or stones. There are two recognised forms of PH. Type I (PH I) is more common and is caused by a functional deficiency of the peroxisomal enzyme, alanine glyoxylate aminotransferase. Phenotypically PH I shows great heterogeneity, ranging from severe infantile oxalosis and death, to milder forms with renal stone disease in later life. Primary hyperoxaluria type II (PH II) is characterised by hyperoxaluria and l-glyceric aciduria, the underlying defects being the result of decreased glyoxylate reductase activity. Patients with PH II have a less severe clinical course than PH I and their predominant clinical feature is nephrolithiasis rather than nephrocalcinosis. With increased awareness of the appropriate tests indicated in patients presenting with hyperoxaluria, more patients with these disorders are currently being diagnosed.18 ,19

Children with small bowel disorders, particularly those affecting the terminal ileum, may present with enteric hyperoxaluria related to increased dietary oxalate absorption. This results from the loss of the normal inhibitory effect of calcium ions, as they are precipitated by the unabsorbed free fatty acids as calcium soaps.

The finding of calcium oxalate stones in older children and adults is often not associated with hyperoxaluria.20

Cystine stones

Cystinuria is an inherited error of defective transport of cystine, lysine, ornithine, and arginine across intestinal and renal tubular cell membranes. Cystine stones occur in children of all ages and have been identified in the newborn period.21 Twenty five per cent of patients pass their first stone during childhood.22 In very young children bladder calculi may occur, but in later childhood renal calculi are more frequent. All cystine calculi are radio-opaque, although at times are not as dense as calcium containing stones, and may sometimes be missed on the plain abdominal film.

Uric acid stones

Uric acid is derived from endogenous sources, as well as from dietary ingestion of purines. Reduced urine volume with dehydration, hyperuricaemia, and a urinary pH that is consistently less than 6 are important factors that influence uric acid stone formation. Uric acid gravel in both kidneys may lead to acute renal failure in the absence of radiological evidence of calculi. This latter complication is less common with the adequate preparation of leukaemia patients undergoing therapy. The inborn errors of purine metabolism are rare, for example, Lesch–Nyhan syndrome (a disorder characterised by self mutilation, hyperuricaemia with uric acid calculi, and choreoathetosis). Uric acid stones have been reported in patients with type I glycogen storage disease, but the mechanism is unclear. Some children, particularly males of Mediterranean background, may present with uric acid stones without hyperuricaemia or uricosuria. It is possible that these children have dihydroxyadenine stones which are not routinely distinguished from uric acid stones, unless specifically requested of the laboratory staff. Dihydroxyadenine stones occur as a result of a deficiency of the enzyme adenine phosphoribosyl transferase. The diagnosis of these cases is important because allopurinol has a satisfactory therapeutic effect and alkalinisation of the urine decreases solubility of the dihydroxyadenine.23

Xanthinuria is a rare condition caused by a deficiency of xanthine oxidase with a resultant failure to convert xanthine to uric acid. The plasma uric acid concentration is therefore very low, but because xanthine is insoluble in acid urine, radiolucent calculi develop. Xanthine calculi should be considered if the parents report an orange/brown sediment in the urine or similar coloured staining of the nappy.24 ,25