Renal tubular malfunction

Kazantzis G, Flynn FV, Spowage JS, Trott DG. Renal tubular malfunction and emphysema in cadmium pigment workers. Quart J Med 1963 32 165-192. 

There have been reports in the literature of hypouricemia coincident with specific inborn metabolic errors, but many of these cases are attributable to defects in the kidney leading to failure of renal tubular reabsorption. It was mentioned above that the excretion of uric acid by the Dalmatian coach hound can be attributed to such a mechanism (Fll). Similarly, the hypouricemia found in the Fanconi syndrome (L4) and Wilson s disease (B12) can be attributed to kidney malfunction. These are not true examples of underproduction of oxypurines, including uric acid, since the daily output of uric acid is normal. The large number of healthy people who have extremely low serum urate values, however, may indicate that there are individuals who underproduce oxypurines but suffer no ill effects because of this. The one well-documented inborn error that results in underproduction of uric acid is xanthinuria. It has been reported in relatively few cases, probably because individuals with this metabolic abnormality who suffer no ill effects would not come to the attention of a physician. 

Nephrotoxicity is primarily accompanied by membrane damage in the renal tubular cells. The biochemical basis for this effect in man is still irat fiilly understood and could be either caused by an effect on lipid metabolism and structure or by mistranslation of proteins inducing malfunctions of membrane traffic (245). The nephrotoxic effect is also seen in neonates when the mother is created during gestation (246), and ir can be suppressed by polyaspartic acid (247). The possible biochemical effects exerted via impairment of translation (or of group 1 intron splicing) in the mitochondria of renal cells remain to be demonstrated. 

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