Calcium oxalate crystal adherence to hyaluronan-, osteopontin-, and CD44-expressing injured/regenerating tubular epithelial cells in rat kidneys

Retention of crystals in the kidney is an essential early step in renal stone formation. Studies with renal tubular cells in culture indicate that hyaluronan (HA) and osteopontin (OPN) and their mutual cell surface receptor CD44 play an important role in calcium oxalate (CaOx) crystal binding during wound healing. This concept was investigated in vivo by treating rats for 1, 4, and 8 d with ethylene glycol (0.5 and 0.75%) in their drinking water to induce renal tubular cell damage and CaOx crystalluria. Tubular injury was morphologically scored on periodic acid-Schiff-stained renal tissue sections and tissue repair assessed by immunohistochemical staining for proliferating cell nuclear antigen. CaOx crystals were visualized in periodic acid-Schiff-stained sections by polarized light microscopy, and renal calcium deposits were quantified with von Kossa staining. HA was visualized with HA-binding protein and OPN and CD44 immunohistochemically with specific antibodies and quantified with an image analyzer system. Already after 1 d of treatment, both concentrations of ethylene glycol induced hyperoxaluria and CaOx crystalluria. At this point, there was neither tubular injury nor crystal retention in the kidney, and expression of HA, OPN, and CD44 was comparable to untreated controls. After 4 and 8 d of ethylene glycol, however, intratubular crystals were found adhered to injured/regenerating (proliferating cell nuclear antigen positive) tubular epithelial cells, expressing HA, OPN, and CD44 at their luminal membrane. In conclusion, the expression of HA, OPN, and CD44 by injured/regenerating tubular cells seems to play a role in retention of crystals in the rat kidney

Lysosomal Modifications in Human Proximal Tubule Induced by Aminoglycoside Treatment: Visualisation by Light Microscopical Cytochemistry

In cryostat sections of kidney biopsies, lysosomes were visualized for light microscopy by staining for acid phosphatase, during 4 incubation times. Twenty patients treated with the antibiotics gentamycin, tobramycin, amikacin or netelmicin during four days were compared to ten untreated control biopsies. Because of the marked heterogeneity of enzyme reaction product throughout the nephron, even within the proximal tubules, the most strongly stained tubular sections were used for comparison. Several enzyme activites created by 5 concentrations of the inhibitor NaF, were differentiated visually; staining intensity increased with incubation time, in all biopies. Treated kidneys display heavier staining than all controls, with the exception of one biopsy; the difference is significant. Biochemical assays of acid phosphatase activity in homogenates have not revealed this difference. The cytochemical method may be used to detect early alterations caused by nephrotoxic drugs. 9 colour light micrographs

Propylene glycol-induced side effects during intravenous nitroglycerin therapy111

Propylene glycol, an alcohol frequently used as a solvent in medical preparations, is considered non-toxic. We found that this solvent, used in a commercially available IV nitroglycerin solution, may cause hyperosmolality, hemolysis and lactic acidosis. The influence of kidney function as the main determinant in causing accumulation of this solvent and consequently hyperosmolality is emphasized. A review of the literature dealing with propylene glycol is given. The possible mechanisms of neurological disturbances occurring during IV nitroglycerin therapy are discussed</p