Genetic versus environmental factors in renal stone disease

The dietary habits of renal stone formers appear to differ from those of the general population. Renal stone formers seem to eat more oxalate, more flesh protein and less vegetable fibres than their normal counterparts. Often their urine volume is low. These are environmental factors which govern nephrolithiasis. Subtle underlying defects are detected not infrequently in these patients; for example, medullary sponge kidneys, abnormally structured macromolecular inhibitors of calcium oxalate crystallization (nephrocalcin and Tamm-Horsfall protein), incomplete distal renal tubular acidosis, deficient activation of pyridoxine, defective intestinal absorption of citrate, excessive production of interleukin-1 by monocytes, subtle primary hyperparathyroidism, heterozygosity for cystinuria, and, discovered more recently, abnormal chloride channels along the nephron. Many of these defects are inheritable, but carriers of the trait are not always active stone formers. The opinion forwarded in this review is that combinations of the environmental and of the underlying or genetic defects are required to trigger renal stone disease.