Abstract
Extract: Proximal renal tubular acidosis has been observed in two infants who had lactic acidosis associated with subacute necrotizing encephalomyelitis. Reduced renal thresholds for bicarbonate (18–19.2 mM/liter) were found in both, in conjunction with the ability to excrete normal quantities of acid. In order to raise the level of serum bicarbonate, increasing rates of infusion of solutions containing bicarbonate were required, because of a progressive increase in serum lactate from 18 to 54 mg/dl. The infusion of sodium bicarbonate expanded the extracellular space, as measured by an increase in chloride space of 12.9%. Volume expansion was associated with a progressive fall in bicarbonate reabsorption from a maximum of 1.91 to 1.02 mM/100 ml glomerular filtration rate. In addition, the tubular reabsorption of phosphate fell from 80 to 60%, urate clearance increased from 8.7 to 20 ml/min/1.73 m2, lactate clearance increased from 0.23 to 22.9 ml/min/1.73 m2, and chloride excretion increased from 0.7 to 3.14 μEq/min/1.73 m2. At autopsy, reduced activity of renal pyruvate carboxylase was demonstrated for the first time in this disease.
Speculation: As a reflection of impaired lactate metabolism in subacute necrotizing encephalomyelitis (SNE), generation of ATP may be reduced in the renal cortex. This reduced supply of energy might be expected to impair reabsorption of normal quantities of filtered bicarbonate; proximal renal tubular acidosis may be the result. The fact that other evidence of proximal tubular dysfunction was not observed in the normohydrated state further suggests that failure to reabsorb filtered sodium bicarbonate may be the initial abnormality observed when the supply of energy diminishes in the renal cortex.
The changes in the chloride space observed during bicarbonate infusions may provide data useful in the interpretation of changes in the renal threshold both for bicarbonate and for other solutes.
Finally, it appears that subacute necrotizing encephalomyelitis may include a spectrum of biochemical abnormalities, and that only certain forms may be associated with renal tubular acidosis.
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Gruskin, A., Patel, M., Linshaw, M. et al. Renal Function Studies and Kidney Pyruvate Garboxylase in Subacute Necrotizing Encephalomyelopathy (Leigh's Syndrome). Pediatr Res 7, 832–841 (1973). https://doi.org/10.1203/00006450-197310000-00007
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DOI: https://doi.org/10.1203/00006450-197310000-00007
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