Abstract
Fanconi syndrome is an enigmatic disorder globally affecting proximal tubule solute handling. Cystinosis is a common cause of this syndrome and is characterized biochemically by increased intracellular cystine. Taking advantage of the ability of CDM to load normal lysosomes with cystine, we examined the effect of this compound on rat renal tubular transport in vivo and in vitro. Normal adult rats were injected with 400 μmoles BID of CDM for 4 days and then urine was collected overnight. There was no difference between controls injected with saline and the treated rats in plasma creatinine, glucose, phosphate, and amino acids except for cystine. Urine volume increased by 133%, as did the excretion of phosphate (42%), glucose (35%) although the actual amount lost was quite low, and α-amino nitrogen (179%) with a generalized aminoaciduria. Renal tissue levels of cystine were not increased but cysteine levels were.
The effect of CDM on isolated rat renal tubule transport was studied by incubating tubules with 2mM CDM for 10 min. removing them from the CDM buffer, and resuspending them in buffer with labeled substrates. CDM markedly inhibited the initial and subsequent uptake of 2mM α-methyl glucoslde, 0.1 mM glycine, 0.1 mM taurine, and 0.025 mM lysine when compared to control tubules handled in a similar fashion without CDM. Both treated and control tubules appeared viable as measured by trypan blue exclusion. Tissue cystine was markedly increased with CDM. These studies indicate that CDM can induce a new model of Fanconi syndrome both in vivo and in vitro.
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Foreman, J., Lee, J., Bowring, M. et al. EFFECT OF CYSTINE DIMETHYLESTER (CDM) ON RENAL TUBULAR FUNCTION, A MODEL OF FANCONI SYNDROME. Pediatr Res 21 (Suppl 4), 341 (1987). https://doi.org/10.1203/00006450-198704010-01044
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DOI: https://doi.org/10.1203/00006450-198704010-01044