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Pulmonary calcification in a renal transplant recipient
Br. J. Dis. Chest (1983)
77, 202
PULMONARY CALCIFICATION IN A RENAL TRANSPLANT RECIPIENT T. W. EVANS,*$ M. COLLINS,* 5 J. E. ADAMS,? P. HOWARD,7 M. FOX,* M. M. PLATTST AND C. B. BROWN* *Royal Hallamshire Hospital, Sheffied and t University of Manchester, Manchester
Metastatic pulmonary calcification has been reported as a post mortem, and rarely as an incidental ante mortem, finding in patients on chronic haemodialysis, and less commonly in renal transplant recipients (Gilman et al. 1980). We describe a patient with a renal transplant in whom diffuse pulmonary calcification was diagnosed ante mortem, and confirmed by computed tomography.
Case Report A 22-year-old male was first seen in 1969 with mesangiocapillary glomerulonephritis which progressed to chronic renal failure. Cadaver renal transplantation was carried out in October 1977 after 2 years of home haemodialysis. After initial technical problems the graft functioned well and the patient had normal renal function until November 1979 when recurrent glomerulonephritis led ultimately to failure of the graft in July 1980. Serum phosphate levels were persistently elevated during this final 7-month period (range 1.53-283mmol/litre), but corrected serum calcium levels were within the normal range (2.12-2.63 mmol/litre). The patient was admitted for haemodialysis in July 1980 and almost immediately developed a pyrexial illness of unknown origin. The chest radiograph (Fig. 1) revealed widespread dense opacities in both lungs, particularly in the upper zones. Previous chest radiographs, the last of which was taken in March 1978, were all normal. Because of the radiographic appearances and the swinging pyrexia in an immunosuppressed, debilitated and uraemic patient, opportunistic fungal infection of the lung was thought to be the most likely diagnosis. Intravenous amphotericin was commenced, although serum fungal precipitins were not detected and a transbronchial lung biopsy showed normal tissue only. Within 72 hours of the start of therapy the patient was apyrexial and clinically much improved and was discharged to home haemodialysis 2 weeks later. The radiographic abnormalities in the lung were unchanged, and whole lung tomography indicated that the opacities were of calcific density. This was confirmed by computed tomography (CT), the attenuation of the deposits being + 108 EU (Fig. 2). A radiographic skeletal survey’showed widespread soft tissue vascular calcification. Pulmonary function tests on discharge and 3 months later showed as the only abnormality a reduced transfer factor of 58% predicted. Eight months after the illness the patient remains well on home dialysis with normal phosphate levels and some regression of the pulmonary calcification. $ Currently at Brompton Hospital, London. 5 Currently at Northern General Hospital, Sheffield. f[ University of Sheffield, Sheffield.
Pulmonary
Calcification
in a Renal Transplant
Recipient
203
Discussion Pulmonary calcification in renal transplant recipients is rarely diagnosed during life. The first report appeared in May 1980 in a patient with normal serum calcium and phosphorus levels and in whom the pulmonary calcification was confirmed by open-lung biopsy (Gilman et al. 1980). S everal factors predisposing to this complication have been suggested, including local tissue injury, hypermagnesaemia and alkalosis during dialysis. Elevated serum phosphate and calcium concentrations secondary to hyperparathyroidism have, however, been claimed to be the most significant of these factors, resulting in the deposition of magnesium
Fig. 1. Chest radiograph, the upper zones
July
1980,
showing
widespread
opacities
in both lungs particularly
in
and calcium phosphate microcrystals in viscera such as heart and lungs and of hydroxyapatite crystals in the walls of blood vessels and periarticular tissue. In tissues already diseased by such processes as caseation, scarring or necrosis there may be no alteration in the levels of calcium and phosphorus in the blood (Heath & Robertson 1977; Hanley & Sherwood 1978). A raised serum phosphate was, however, present in our patient in the 7 months before the radiographic changes were noted. Parathormone assays were not done and it is not known when the deposits developed, as there was a long interval between successive chest radiographs. Deposition of calcium in sites of tissue damage due to previous infection
204
T. W. Evans et al.
is reported (Hanley & Sherwood 1978) although the short interval between the onset of the pyrexial illness and the demonstration of the calcium deposition makes this aetiology unlikely in our patient. Pulmonary calcification is a rare complication in patients with chronic renal failure and is usually only diagnosed at post mortem. In a prospective study of 3 1 patients on chronic haemodialysis, parenchymal lung calcification was found in nine out of 15 patients at post mortem but was evident radiographically in only one (Conger et al. 1978). This difficulty in recognizing pulmonary calcification radiologically may be caused by various factors. Frequently in such patients there are associated confusing opacities in the lungs, related to infection or oedema, or
Fig. 2. CT scan through the upper thorax more extensive on the right
with pulmonary
calcification
(attentuation
+ 108 EU)
the clinical condition of the patient precludes obtaining the high quality departmental radiographs necessary to demonstrate small areas of calcification. Scinitigraphy using bone-seeking radionuclides has proved a sensitive method of detecting calcification in the lung before it is evident radiographically (Faubert et al. 1980), but it is not specific, and malignant effusions and lymphoma may give falsepositive results (Holmes 1979). I n our patient computed tomography (CT) confirmed that the pulmonary opacities contained calcium. CT may prove to be a more sensitive method than a chest radiograph for detecting such pulmonary calcification, if the calcium is deposited in aggregates of at least 1-2 mm in size so as to fill one whole picture element (of the order of 1 mm x 1 mm). However,
Pulmonary
Calcification
in a Renal Transplant
Recipient
205
microcalcification deposited in well-separated crystals may not be as well detected by CT as by a good chest radiograph. There is a close correlation in patients on chronic dialysis between the extent of pulmonary calcification and severity of respiratory abnormalities, including changes in vital capacity, carbon monoxide diffusing capacity and arterial oxygen levels (Conger et al. 1978). I n our patient, transfer factor only was reduced, an abnormality which can occur anyway in chronic renal failure. There are few reports of regression of the pulmonary calcification, as has occurred in this patient (McLachlan et al. 1968).
References Conger, J. D., Hammond, W. S., Alfrey, A. C., Contiguglia, S. R., Stanford, R. E. & Huffer, W. E. (1978) Pulmonary calcification in chronic dialysis patients. Ann. intern. Med. 83, 330-336. Faubert, P. F., Shapiro, W. B., Porush, J. G., Chou, S. Y., Gross, J. M., Bondi, E. & GomezLeon, G. (1980) Pulmonary calcification in haemodialysed patients detected by technetium - 9grn diphosphonate scanning. Kidney International 18, 95-102. Gilman, M., Nissim, J., Terry, P. & Welton, A. (1980) Metastatic pulmonary calcification in the renal transplant recipient. Am. Rev. resp. Dis. 121, 415-419. Hanley, D. A. & Sherwood, L. M. (1978) Secondary hyperparathyroidism in chronic renal failure. Med. Clins N. Am. 62, 1219-1388. Heath, D. & Robertson, J. A. (1977) Pulmonary cakinosis. Thorax 32, 606-611. Holmes, R. A. (1979) Detection of diffuse metastatic calcification with radiostrontium. J. nut. Med. II, 327-328. McLachlan, M. S. F., Wallace, M. & Seneviratne, C. (1968) Pulmonary calcification in renal failure. Report of three cases. Br. J. Radiol. 41, 99-106.
77, 202
PULMONARY CALCIFICATION IN A RENAL TRANSPLANT RECIPIENT T. W. EVANS,*$ M. COLLINS,* 5 J. E. ADAMS,? P. HOWARD,7 M. FOX,* M. M. PLATTST AND C. B. BROWN* *Royal Hallamshire Hospital, Sheffied and t University of Manchester, Manchester
Metastatic pulmonary calcification has been reported as a post mortem, and rarely as an incidental ante mortem, finding in patients on chronic haemodialysis, and less commonly in renal transplant recipients (Gilman et al. 1980). We describe a patient with a renal transplant in whom diffuse pulmonary calcification was diagnosed ante mortem, and confirmed by computed tomography.
Case Report A 22-year-old male was first seen in 1969 with mesangiocapillary glomerulonephritis which progressed to chronic renal failure. Cadaver renal transplantation was carried out in October 1977 after 2 years of home haemodialysis. After initial technical problems the graft functioned well and the patient had normal renal function until November 1979 when recurrent glomerulonephritis led ultimately to failure of the graft in July 1980. Serum phosphate levels were persistently elevated during this final 7-month period (range 1.53-283mmol/litre), but corrected serum calcium levels were within the normal range (2.12-2.63 mmol/litre). The patient was admitted for haemodialysis in July 1980 and almost immediately developed a pyrexial illness of unknown origin. The chest radiograph (Fig. 1) revealed widespread dense opacities in both lungs, particularly in the upper zones. Previous chest radiographs, the last of which was taken in March 1978, were all normal. Because of the radiographic appearances and the swinging pyrexia in an immunosuppressed, debilitated and uraemic patient, opportunistic fungal infection of the lung was thought to be the most likely diagnosis. Intravenous amphotericin was commenced, although serum fungal precipitins were not detected and a transbronchial lung biopsy showed normal tissue only. Within 72 hours of the start of therapy the patient was apyrexial and clinically much improved and was discharged to home haemodialysis 2 weeks later. The radiographic abnormalities in the lung were unchanged, and whole lung tomography indicated that the opacities were of calcific density. This was confirmed by computed tomography (CT), the attenuation of the deposits being + 108 EU (Fig. 2). A radiographic skeletal survey’showed widespread soft tissue vascular calcification. Pulmonary function tests on discharge and 3 months later showed as the only abnormality a reduced transfer factor of 58% predicted. Eight months after the illness the patient remains well on home dialysis with normal phosphate levels and some regression of the pulmonary calcification. $ Currently at Brompton Hospital, London. 5 Currently at Northern General Hospital, Sheffield. f[ University of Sheffield, Sheffield.
Pulmonary
Calcification
in a Renal Transplant
Recipient
203
Discussion Pulmonary calcification in renal transplant recipients is rarely diagnosed during life. The first report appeared in May 1980 in a patient with normal serum calcium and phosphorus levels and in whom the pulmonary calcification was confirmed by open-lung biopsy (Gilman et al. 1980). S everal factors predisposing to this complication have been suggested, including local tissue injury, hypermagnesaemia and alkalosis during dialysis. Elevated serum phosphate and calcium concentrations secondary to hyperparathyroidism have, however, been claimed to be the most significant of these factors, resulting in the deposition of magnesium
Fig. 1. Chest radiograph, the upper zones
July
1980,
showing
widespread
opacities
in both lungs particularly
in
and calcium phosphate microcrystals in viscera such as heart and lungs and of hydroxyapatite crystals in the walls of blood vessels and periarticular tissue. In tissues already diseased by such processes as caseation, scarring or necrosis there may be no alteration in the levels of calcium and phosphorus in the blood (Heath & Robertson 1977; Hanley & Sherwood 1978). A raised serum phosphate was, however, present in our patient in the 7 months before the radiographic changes were noted. Parathormone assays were not done and it is not known when the deposits developed, as there was a long interval between successive chest radiographs. Deposition of calcium in sites of tissue damage due to previous infection
204
T. W. Evans et al.
is reported (Hanley & Sherwood 1978) although the short interval between the onset of the pyrexial illness and the demonstration of the calcium deposition makes this aetiology unlikely in our patient. Pulmonary calcification is a rare complication in patients with chronic renal failure and is usually only diagnosed at post mortem. In a prospective study of 3 1 patients on chronic haemodialysis, parenchymal lung calcification was found in nine out of 15 patients at post mortem but was evident radiographically in only one (Conger et al. 1978). This difficulty in recognizing pulmonary calcification radiologically may be caused by various factors. Frequently in such patients there are associated confusing opacities in the lungs, related to infection or oedema, or
Fig. 2. CT scan through the upper thorax more extensive on the right
with pulmonary
calcification
(attentuation
+ 108 EU)
the clinical condition of the patient precludes obtaining the high quality departmental radiographs necessary to demonstrate small areas of calcification. Scinitigraphy using bone-seeking radionuclides has proved a sensitive method of detecting calcification in the lung before it is evident radiographically (Faubert et al. 1980), but it is not specific, and malignant effusions and lymphoma may give falsepositive results (Holmes 1979). I n our patient computed tomography (CT) confirmed that the pulmonary opacities contained calcium. CT may prove to be a more sensitive method than a chest radiograph for detecting such pulmonary calcification, if the calcium is deposited in aggregates of at least 1-2 mm in size so as to fill one whole picture element (of the order of 1 mm x 1 mm). However,
Pulmonary
Calcification
in a Renal Transplant
Recipient
205
microcalcification deposited in well-separated crystals may not be as well detected by CT as by a good chest radiograph. There is a close correlation in patients on chronic dialysis between the extent of pulmonary calcification and severity of respiratory abnormalities, including changes in vital capacity, carbon monoxide diffusing capacity and arterial oxygen levels (Conger et al. 1978). I n our patient, transfer factor only was reduced, an abnormality which can occur anyway in chronic renal failure. There are few reports of regression of the pulmonary calcification, as has occurred in this patient (McLachlan et al. 1968).
References Conger, J. D., Hammond, W. S., Alfrey, A. C., Contiguglia, S. R., Stanford, R. E. & Huffer, W. E. (1978) Pulmonary calcification in chronic dialysis patients. Ann. intern. Med. 83, 330-336. Faubert, P. F., Shapiro, W. B., Porush, J. G., Chou, S. Y., Gross, J. M., Bondi, E. & GomezLeon, G. (1980) Pulmonary calcification in haemodialysed patients detected by technetium - 9grn diphosphonate scanning. Kidney International 18, 95-102. Gilman, M., Nissim, J., Terry, P. & Welton, A. (1980) Metastatic pulmonary calcification in the renal transplant recipient. Am. Rev. resp. Dis. 121, 415-419. Hanley, D. A. & Sherwood, L. M. (1978) Secondary hyperparathyroidism in chronic renal failure. Med. Clins N. Am. 62, 1219-1388. Heath, D. & Robertson, J. A. (1977) Pulmonary cakinosis. Thorax 32, 606-611. Holmes, R. A. (1979) Detection of diffuse metastatic calcification with radiostrontium. J. nut. Med. II, 327-328. McLachlan, M. S. F., Wallace, M. & Seneviratne, C. (1968) Pulmonary calcification in renal failure. Report of three cases. Br. J. Radiol. 41, 99-106.