Frochot V, Jouanneau C, Letavernier E, Haymann JPh, Bazin D, Daudon M.
Service des Explorations Fonctionnelles, Hôpital Tenon, APHP, Paris, France INSERM UMR S 1155, Hôpital Tenon, Paris, France LCMCP, CNRS, Collège de France, Paris, France.
Background: Biopsies of native or transplanted kidneys in patients suffering chronic or acute renal failure are commonly stained for tissue examination and search for possible crystal deposits which are then identified by polarizing microscopy and staining by von Kossa’s method revealing mainly calcium (Ca) deposits. Aim of the study Revisiting the nature of crystal deposits in kidney tissue sections by infrared microscopy.
Method: 25 renal biopsies presumably containing crystal deposits were analyzed with the Spotlight 400 FTIR imaging System in the mid infrared spectral range to obtain infrared maps of tissue slides at high spatial resolution, down to 10 microns. When required, an optional ATR imaging accessory was used, improving the spatial resolution by a factor four, down to 3 microns at 1000 cm-1.
Results: Among the 25 biopsies, 18 (72%) contained crystals accurately characterized by histologic examination in only 10 cases (40%). Nine crystalline species were observed. In 6 cases, two different species were identified: -Ca oxalate monohydrate (COM) (n=7), - COM and Ca oxalate dehydrate (n=1), -COM and dihydroxy-adenine (n=1), -carbapatite (CA) and amorphous carbonated Ca phosphate (ACCP) (n=3), -Sodium hydrogen urate monohydrate (n=1), - Drugs (n=2): foscarnet (+CA), atazanavir, -Lipids (n=3): cholesterol esters. In addition, we found large protein deposits within tubules lumen in 3/7 other biopsies. Only 12% of patients had reversible renal failure. In the case of foscarnet-induced renal failure, two types of crystals were found in different parts of the nephron: phosphoformiate trisodium crystals within glomerules and CA in the proximal tubular cells.
Discussion: In 72% of biopsies, we identified and quantified crystalline species including non Cacontaining deposits in 28% of cases. Identification of dihydroxyadenine prompted to treat the patient with allopurinol, thus allowing a total recovery of the grafted kidney function. Beyond the diagnostic aspect, the concomitant presence of foscarnet and Ca phosphate salt, a possible metabolite of the drug, could suggest a phosphoformiate metabolism in the kidney.
Conclusion: A precise identification of crystal deposits in the kidney tissue may be essential for the diagnosis of an unexplained renal failure. Common histological procedures clearly fail to identify accurately crystals deposits. In most cases, light and polarizing microscopic examination should be completed by infrared analysis.