Contribution to the phosphate-induced nephropathy in the dog. Comparative light and electron microscopic investigations on the proximal tubule after oral application of K2HPO4, Na2HPO4, KCl and NaCl.

20 male beagle-dogs divided into 4 groups were given equimolar amounts of K2HPO4, Na2HPO4, KCl and NaCl daily by gavage over a period of 9 or 22 weeks. A further collective of 5 dogs served as the control. After terminating the experiment the animals were killed and the kidneys were investigated by light- and electron microscopy. No renal damage developed in dogs treated with KCl or NaCl. In those treated with K2HPO4 or Na2HPO4 nephrocalcinosis with disseminated atrophy of the proximal tubule occurred. The following processes in the proximal tubulus could be analysed and pathogenetically classified: the dedifferentiated tubulus epithelial cells undergo advancing autodigestion by multiplication, enlargement and fusion of autophagic vacuoles and autophagolysosomes. After extrusion of the lysosomal bodies into the tubular lumen and the degradation of the intratubular detritus, residues consisting of completely empty and collapsed basement membrane tubes remain. The significance of these findings for clinical diagnostics in relation to the urine is discussed. It is emphasized that, in the case of proven tubulopathy with a negative protein finding and an absence of epithelial cells and casts in the urine, it can be assumed that the protein and epithelial cells were digested intratubularly by lysosomal enzymes.