Standardized staining procedures for histopathology are the gold standard to reveal ectopic calcifications. Typically, tissue samples are taken from patients and stained for examination by pathologists. Several publications have underlined the limitations of this procedure. Bonnewald et al [ Bonewald L F, Harris S E, Rosser J, Dallas M R, Dallas S L, Camacho N P, Boyan B and Boskey A 2003 Calcif. Tissue Int. 72 537–47] demonstrated that staining procédures such as von Kossa staining alone is not appropriate for identifying and quantifying apatite. Identification can be completed by other techniques routinely used in some cases: Fourier transform infrared (FTIR)61 and Raman spectroscopy.
In fact, crystals are found in kidney biopsies performed in order to understand the mechanism of the loss of renal function. However, only few histochemical tests are available to attempt an identification of the crystals. Moreover, in some cases, common crystals such as calcium oxalate monohydrate may be present as a consequence of renal failure, but they are not involved in the kidney loss. For these reasons, it is of clinical importance to accurately identify crystals found in the tissue as they can help to early characterization of a disease,
In a recent investigation, new crystalline phases were described such as amorphous silica, sodium hydrogen urate, methyl-1 uric acid and three different Ca2+ phosphates namely whitlockite, OCP and ACCP. Moreover, for the first time, we underline the chemical heterogeneity of intratissular calcifications.
Note that Dihydroxyadenine crystals were found in four patients (five biopsies in Table 1). Such crystals deposits in parenchyma are pathognomonic of a rare disease, adenine phosphoribosyltransferase deficiency, an inherited disease able to induce recurrent kidney stones and/or kidney failure. Dihydroxyadenine is often too late identified in patients who have developedrenal insufficiency and sometimes after the crystal-induced destruction of a kidney transplant.
Kenneth,
Thanks for answer. In fact, i try to show that anatomopathologists have other opportunitities to perform their jobs. In the case of kidney biopsy, new experimental set ups ( Perkin Elmer FTIR device for example) can clearly give a completely new set of information which can change the life of patients. At this point, patients can loss their kidney functions because FTIR measurments have not been performed. Hospitals can have big trouble and justice problems. I think that each hospital which deals with kidney biopsy must have a FTIR device.
By the way, XRD can give the right answer but note that in the some cases mineral deposits can be made of amorphous compounds.
Take care
Dominique
Kenneth,
You are right. We have to perform also TEM (along with FTIR) to perform significant analysis of biopsy. Do you you think nanoFTIR can bring information on micelle ?
take care
Dominique
I don't really understand the link with kidney biopsy ? Do you think of a particular pathology?
Take care
Dominique
It is ok. sometimes calcifications have exogeneous origin.
Take care
Dominique
Calcifications containing amorphous Silica for example (M Augusti, J C Mikaelian, H Monsaint, D Brin, M Daudon (1993) A silica urinary calculus secondary to the absorption of gelopectose in a child Prog Urol 3: 5. 812-815 Oct ) or deposits coming from drugs (Michel Daudon, Paul Jungers (2004) Drug-induced renal calculi: epidemiology, prevention and management. Drugs 64: 3. 245-275; )
take care
Dominique
Kenneth,
Sorry for the définitions. As you know, different drugs have been removed from the market due to crystallzation processes for which you don't need endocytosis. A lot of research has to be perform, FTIR spectroscopy is not really used at the hospitals.
Take care
Dominique
We have recently investigated through high spatial resolution infrared spectroscopy the kidney distribution of some poorly soluble drugs and metabolites. It is well known that foscarnet crystallizes in glomeruli. Foscarnet (phosphonoformic acid) is a pyrophosphate analogue that inhibits the DNA polymerase of all herpes viruses, which is commonly used in immuno-suppressed patients (AIDS, grafted patients) who developed CMV infection. Through SR-m FTIR, spectroscopy we observed sodium foscarnet crystals in glomeruli in line with a previous study. In addition, we found in the cells of the proximal tubule an accumulation of apatite crystals suggesting that the drug is locally metabolized by splitting the bond between the two phosphate residues of foscarnet. To the best of our knowledge, no data has been reported about associated crystalline phases deposited within the cells of the tubules.
Take care
Dominique
Kenneth,
In kidney biopsy, the presence of calciication is always pathologic. For this pateint, an simple explanation was given by the presence of foscarnet in the glomeruli. We have just started a study on kidney biopsy. I will send you the paper ASAP.
Take Care
Dominique
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