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Diagnosis: Nephrocalcionosis

Nephrocalcinosis is a condition in which calcium levels in the kidneys are increased. This increase can be detected (usually as an incidental finding) through a radiologic exam or via microscopic examination of the renal tissues. The term nephrocalcinosis most often applies to a generalized increase in renal calcium content, as opposed to the localized increase observed in calcified focal lesions. (Fulop T, Agraharkar M, Patel R. Nephrocalcinosis. In eMedicine. [Link])

There are four mechanisms of lymphoma-related hypercalcemia (as in the case presented): (1) PTHrp mediated humoral hypercalcemia; (2) tumor production of vitamin D analogues; (3) ectopic secretion of PTH from tumors; (4) osteolytic bone destruction. Humoral hypercalcemia is the most common mechanism. Cytokines including tumor necrosis factor, IL-1, IL-6, macrophage inflammatory protein 1-alpha, and lymphotoxin can stimulate macrophages differentiation into osteoclasts thereby causing bone destruction and hypercalcemia (Chang PY, et al. Acute renal failure due to hypercalcemia-related nephrocalcinosis in a patient of non-Hodgkin's lymphoma featuring swelling of bilateral kidneys. Ann Hematol. 2008;87:489-90. [PubMed link]).

Microscopic nephrocalcinosis is characterized by the presence of microscopic crystalline calcium precipitates in the form of oxalate and/or phosphate. Patients with macroscopic nephrocalcinosis have larger areas of calcifications, which can be observed on visual or radiologic examination without further magnification.

Nephrocalcinosis has a significant overlap with hypercalcemia, nephrolithiasis, renal parenchymal damage, and reduced renal function. Therefore, rather being considered a single, distinct disease process, it should be viewed as a helpful finding for several distinct disease processes, demanding further evaluation.

Patients with hypercalcemia develop renal function abnormalities. The cytoplasmic concentration of calcium is tightly regulated and kept very low, being maintained by active extracellular extrusion of calcium and sequestration into the endoplasmic reticulum and mitochondria. Increased extracellular calcium leads to impairment of the calcium messenger system with gross tubular impairment. Hypercalcemia results in renal vasoconstriction and a reduced glomerular filtration rate. It also interferes with renal tubular functions. Impaired renal concentration ability and resistance to vasopressin are the most common defects observed with hypercalcemia. This may be mediated by reduced sodium transport in the loop of Henle and by antidiuretic hormone antagonism via calcium-sensing receptors, or it may be related to medullary prostaglandin synthesis (Fulop T, Agraharkar M, Patel R. Nephrocalcinosis. In eMedicine. [Link]).

At biopsy, it can be evidenced early stone formation, with blockage of the collecting tubes and subsequent inflammatory response. At autopsy, there are microscopic deposits of calcium in the renal medulla. Different patterns of microscopic nephrocalcinosis have been described. Cortical calcification has been found after parenteral calcium administration. The corticomedullary type involves calcium phosphate deposits that occur in the inner zone of the renal cortex and extend into the medulla, as in the present case.

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Bibliography

• Miller NL, Humphreys MR, Coe FL, Evan AP, Bledsoe SB, Handa SE, Lingeman JE. Nephrocalcinosis: re-defined in the era of endourology. Urol Res. 2010;38(6):421-7. [PubMed link]
• Fulop T, Agraharkar M, Patel R. Nephrocalcinosis. In eMedicine. [Link]. Consulted: February 2, 2011.
• Ammenti A, Pelizzoni A, Cecconi M, Molinari PP, Montini G. Nephrocalcinosis in children: a retrospective multi-centre study. Acta Paediatr. 2009;98(10):1628-31. [PubMed link]
• Vervaet BA, Verhulst A, D'Haese PC, De Broe ME. Nephrocalcinosis: new insights into mechanisms and consequences. Nephrol Dial Transplant. 2009;24(7):2030-5. [PubMed link]
• Chang PY, Lee SH, Chao TK, Chao TY. Acute renal failure due to hypercalcemia-related nephrocalcinosis in a patient of non-Hodgkin's lymphoma featuring swelling of bilateral kidneys. Ann Hematol. 2008;87(6):489-90. [PubMed link]
• Kummeling MT, de Jong BW, Laffeber C, Kok DJ, Verhagen PC, van Leenders GJ, van Schaik RH, van Woerden CS, Verhulst A, Verkoelen CF. Tubular and interstitial nephrocalcinosis. J Urol. 2007;178(3 Pt 1):1097-103. [PubMed link]

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