Unclear radiographic pulmonary changes in a patient who recently underwent renal transplantation
(Section Editor: K. Kühn)
Jan Rabe1,
Peter Schnülle2,
Steffen J. Diehl1,
Dietmar Lorenz3,
Fokko J. van der Woude2 and
Max Georgi
1 Department of Clinical Radiology,
2 Department of Internal Medicine V (Nephrology/Endocrinology) and
3 Department of Surgery, University Hospital Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer, Mannheim, Germany
Keywords: computed tomography; hyperparathyroidism; metastatic calcification; renal transplantation
Case
A 35-year-old patient with end-stage renal disease due to reflux nephropathy was admitted to hospital to receive a first cadaveric renal transplantation (NTX). The patient had been on chronic haemodialysis for more than 6 years with signs of a secondary hyperparathyroidism (Table 1
), which was treated by calcitriol replacement, calcium carbonate, and restriction of dietary phosporus intake.
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Table 1. Laboratory findings of calcium, PTH and phosporous in a patient who had been on chronic haemodialysis for 6 years
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On admission, physical examination and routine chest radiography (Figure 1
) were normal. Laboratory findings of iPTH, serum calcium, and phosphorus are presented in Table 1
. The alkaline phosphatase level was elevated (363 U/l).
Renal transplantation was performed uneventfully on the day of admission. The post-operative period was complicated by delayed graft function requiring haemodialysis during first 3 weeks. Immunosuppressive medication consisted of a triple drug therapy including cyclosporin, mycophenolate mofetil, and steroids. A renal core biopsy (serum creatinine 14.0 mg/dl) was performed on the eighth day post-transplant, showing moderate interstitial lymphocyte infiltration with tubulitis. Thus, rejection therapy with high-dose steroids was initiated. As urine output remained diminished a re-biopsy (serum creatinine 14.1 mg/dl) was taken on the eighteenth post-operative day revealing the predominant finding of acute tubular necrosis. As scattered lymphocyte infiltrates were still noted within the interstitium, the cyclosporin dose was reduced by 50% and antithymocytic globulin (ATG) was taken into consideration for treatment of steroid-resistant rejection.
On the same day a chest radiograph, which was obtained to control the position of a central line, revealed a right basal paracardial infiltration (Figure 2
). Despite the lack of symptomsthe patient complained neither of fever, cough nor of sputum production antibiotic therapy with ceftriaxone was started and ATG was withheld due to suspicion of asymptomatic bacterial pneumonia under immunosuppression.
A chest radiograph 6 days later (Figure 3a
) showed an increase of the infiltrative pulmonary changes, which were now found bilateraly. Furthermore, the lateral view demonstrated that these infiltrates were exclusively located in the anterior third of both lungs (Figure 3b
). This very unusual distribution, and the discrepancy between radiological findings and unremarkable physical examination, prompted further investigation by unenhanced computed tomography which revealed an excessive calcification of lung parenchyma (Figure 4
). The diagnosis of pulmonary metastatic calcification was made, and urgent parathyroidectomy was performed. The patient recovered uneventfully from the operation. The serum creatinine level on discharge from hospital was 2.6 mg/dl. A chest radiography 4 months after renal transplantation showed no further progression of the pulmonary calcifications.

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Fig. 3. Chest radiographs (a: anterior and b: lateral view) 24 days after renal transplantation: increase of the pulmonary infiltrates which are exclusively located in the anterior third of both lungs.
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Discussion
Metastatic calcification of lung parenchyma is most often caused by hypercalcaemia due to a variety of disorders, including primary and secondary hyperparathyroidism, extensive bone malignancy, and hypervitaminosis D. In 1855, Rudolf Virchow was the first to describe the connection between metastatic calcifications and chronic renal failure, which is the most common underlying condition [1]. There are few reports of patients without any disturbances of calcium and phosphorus metabolism [2,3]. Hypercalcaemia, however, and elevation of the calciumxphosporus product seem to play the most important role in the development of metastatic calcification. With respect to the lung, pre-existing parenchymal changes may be an additional factor [4]. As the variation of pH from 7.35 to 7.45 decreases phosphocalcific salt solubility by 10%, alkaline conditions favour calcification. Seyle et al. [10] described a more complex course of calcification with a poor prognosis. In this condition, known as systemic calciphylaxis, not only the lungs are affected by calcification, but other organs such as skinleading to severe skin necroseskidneys, heart, and mucus membranes.
Symptoms can vary from an absolute asymptomatic courseas in our patientmild or moderate respiratory distress [5], to life-threatening or fatal respiratory failure which is seen mainly in renal transplant patients with pre-existing hyperparathyroidism [68]. The time of onset of this fulminant calcification varies. It is described as occurring immediately [6,8] or even years after renal transplantation [9].
Because of the potentially fatal course, progressive metastatic calcification of the lungs should be treated without delay once it is recognized. Treatment should be directed against the underlying cause of hypercalcaemia. In patients with hyperparathyroidism due to chronic renal failure parathyroidectomy is the treatment of choice.
Although pulmonary calcifications are reported in about 80% of patients with end-stage renal disease [11], antemortem radiographic detection is rare. If visible, the radiographic pattern can have various forms: focal airspace consolidation, mimicking pneumonia or infarction; nodular infiltrates or diffuse interstitial infiltrates, eventually mimicking pneumonia or pulmonary oedema [2,12]. The calcific nature of these changes is rarely identified on conventional chest radiographs, whereas computed tomography is able to detect even small amounts of calcium [5]. Because the higher ventilationperfusion ratio in the upper lung (in the anterior lung in a supine position) results in increased alkalinity, calcification is predominantly seen at these sites [6].
Teaching point
The development of pulmonary infiltrates in renal transplant patients should lead to further investigation without delay, especially if the nature of the infiltration is unclear. Unenhanced computed tomography is able to confirm or rule out metastatic calcification, which is a rare but potentially fatal complication in renal transplant recipients.
Notes
Supported by an educational grant from

Fresenius Medical Care
Correspondence and offprint requests to: Jan Rabe, MD, Department of Clinical Radiology, University Hospital Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer, D-68167 Mannheim, Germany. 
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