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Nephrol Dial Transplant (2012) 27: 1122–1131 doi: 10.1093/ndt/gfr414 Advance Access publication 29 July 2011
Histopathological patterns of nephrocalcinosis: a phosphate type can be distinguished from a calcium type
Thorsten Wiech1,2, Helmut Hopfer3, Ariana Gaspert4, Susanne Banyai-Falger5, Martin Hausberg6, Josef Schro¨der7, Martin Werner2 and Michael J. Mihatsch3
1Centre of Chronic Immunodeficiency, University Medical Center Freiburg, University of Freiburg, Freiburg, Germany, 2Institute of Pathology, University Hospital Freiburg, Freiburg, Germany, 3Institute for Pathology, University Hospital Basel, Basel, Switzerland, 4Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland, 5Klinik St Anna, Luzern, Switzerland, 6Sta¨dtisches Klinikum Karlsruhe, Karlsruhe, Germany and 7Institute of Pathology, University Hospital Regensburg, Regensburg, Germany Correspondence and offprint requests to: Thorsten Wiech; E-mail: [email protected]
Abstract different chemical composition, such as calcium oxalate or Background. The etiology of nephrocalcinosis is variable. calcium phosphate, and can, but does not have to be associ- In this study, we wanted to elucidate whether the histopa- ated with nephrolithiasis. Pathologists distinguish between thological appearance of calcium phosphate deposits oxalosis and nephrocalcinosis, the latter again covering dif- provides information about possible etiology. ferent compositions but excluding calcium oxalate. Tradi- Methods. Autopsy cases from the years 1988 to 2007 and tionally, pathologists used the term ‘calcium nephrosis’ for native kidney biopsies from a 50-year period (1959–2008) dystrophic calcification i.e. calcification of necrosis and the with nephrocalcinosis were identified. The biopsy cases term ‘nephrocalcinosis’ for metastatic calcification [1]. In our were re-evaluated by light microscopy. The autopsy cases study, we defined nephrocalcinosis as metastatic renal calci- were analysed according to the underlying disease. The bi- fications (excluding oxalosis) by histopathological detection opsy cases were grouped with respect to the likely etiology of calcium deposits without associated tissue necrosis. of nephrocalcinosis. Total number, density, localization, Nephrocalcinosis can be classified according to the local- size and pattern of all calcification foci were documented ization of the deposits: calcium can precipitate predomi- and correlated with clinical and laboratory data. nantly in the medulla, as for example in the medullary Results. About 223 of 12 960 autopsy cases (1.7%) had sponge kidney. Calcifications mainly located in the renal nephrocalcinosis, 111 of which (49.8%) suffered from ad- cortex are found, for example, in cortical necrosis. In con- vanced malignant tumours. Nephrocalcinosis was the main trast to ultrasonography or computed tomography, light mi- diagnosis in 48 of 12 480 native kidney biopsies (0.4%). croscopy can further distinguish whether calcifications are Clinicopathological correlation revealed a specific pattern localized in the tubular lumens, tubular epithelium, tubular of calcification associated with hyperphosphataemia and/or basement membrane or in interstitial space [2]. On the other hyperphosphaturia: these cases showed predominant glob- hand, nephrocalcinosis can be classified according to the ular or shell-like calcifications (phosphate type). In con- chemical composition, which is likely associated with the trast, the biopsies of the hypercalcaemic/hypercalciuric etiology of renal calcification. Typically, calcium precipi- group had a different predominant pattern with clumpy or tates with anions in the kidney forming calcium oxalate or finely granular calcifications (calcium type). calcium phosphate (as hydroxyl apatite) deposits. Conclusions. Our results indicate that hyperphosphaturia- Renal calcium deposits occur (i) in disorders associated associated cases of nephrocalcinosis can be distinguished with impaired homeostasis and an increased renal excretion from hypercalciuria-associated cases histopathologically. of calcium or phosphate or (ii) by an altered solubility, e.g. Keywords: colonoscopy; histopathology; hypercalciuria; due to a locally altered pH value in the course of renal hyperphosphaturia; nephrocalcinosis tubular acidosis, hypocitraturia or tissue necrosis. Apart from that, factors facilitating crystal adhesion to the tubular epithelium seem to be a prerequisite for nephrocalcinosis [3–5]. Hypercalciuria can occur with hypercalcaemia (see Introduction Table 1, e.g. in primary hyperparathyroidism, elevated vi- tamin D3, sarcoidosis) or with normal serum calcium levels Nephrocalcinosis is a clinical term defined as the renal (idiopathic hypercalciuria). In analogy, hyperphosphaturia deposition of calcium. This definition includes deposits of can be associated with hyperphosphataemia or with normal