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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2016  |  Volume : 27  |  Issue : 5  |  Page : 1037-1042
Severe metastatic calcifications in a hemodialysis patient


1 Department of Internal Medicine, Military Hospital, Mont Fleury, Tunis, Tunisia
2 Intensive Care Unit, Military Hospital, Mont Fleury, Tunis, Tunisia

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Date of Web Publication22-Sep-2016
 

   Abstract 

Tissue calcification is a common complication in patients on continuous hemodialysis (HD) for chronic renal failure; however, severe calcification is unusual. Three distinct clinical types of extraosseous calcifications are found in uremic patients: vascular calcification, periarticular (tumoral) calcification, and visceral calcification (heart, lung, and kidney). We report a case of a young chronic HD patient who presented with extensive metastatic calcifi cations both vascular, visceral specially localized in the lungs, and periarticular with progressively increasing multiple subcutaneous swellings. This evolution was secondary to noncompliance of the patient to the treatment of a malignant hyperparathyroidism with a marked elevation of phosphocalcium product.

How to cite this article:
Labidi J, Ariba YB, Gabsia AB, Ajili F, Battikh R, Louzir B, Abdelhafidh NB, Othman SI. Severe metastatic calcifications in a hemodialysis patient. Saudi J Kidney Dis Transpl 2016;27:1037-42

How to cite this URL:
Labidi J, Ariba YB, Gabsia AB, Ajili F, Battikh R, Louzir B, Abdelhafidh NB, Othman SI. Severe metastatic calcifications in a hemodialysis patient. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2020 Oct 28];27:1037-42. Available from: https://www.sjkdt.org/text.asp?2016/27/5/1037/190884

   Introduction Top


Soft tissue and vascular calcifications are commonly present in uremic patients due to disturbances in calcium and phosphate balance and also, hyperparathyroidism. [1] However, visceral calcifications are serious and uncommon complications of end-stage renal disease. They can contribute to the increased risk of morbidity and mortality among chronic kidney disease patients.

We report a case of a male hemodialysis (HD) patient who developed uncontrolled hyperparathyroidism rapidly within one year after commencing HD therapy, with clinical presentations of tumoral calcinosis, vascular and pulmonary calcifications responsible of an acute respiratory insufficiency.


   Case Report Top


A 19-year-old man underwent HD treatment since March 2010 because of end-stage renal failure secondary to reflux nephropathy due to a hypocompliant areflexic neurogenic bladder. His first phosphocalcic parameters showed calcium at 1.39 mmol/L, phosphorous at 4.8 mmol/L, and parathyroid hormone (PTH) at 2679 pg/mL. He was treated by regular HD and oral calcium carbonate. His compliances to oral medications and appropriate diet of chronic kidney disease were poor.

Initially, he was asymptomatic for one year, but in 2012, he consulted us because of progressively enlarging painful subcutaneous mass localized next the left elbow and the joints of the two hands and a deterioration of general state with anorexia and weight loss. Radiographic investigations showed extensive periarticular calcifications [Figure 1]. Biochemical parameters showed hypercalcemia at 2.63 mmol/L and hyperphosphatemia at 3.17 mmol/L. A low calcium diet and noncalcium-containing phosphate binder Sevelamer ® were prescribed. However, his noncompliance to medications continued and became even worse. His PTH level increased markedly (PTH at 2890 pg/mL) and his calcium-phosphate product remained elevated (13 mmol [2] /L [2] , normal value = 5.8 mmol [2] /L [2] . Parathyroid echography and sestamibi parathyroid scintiscan were reported normal. Parathyroidectomy was advised for refractory hyperparathyroidism, but the patient refused.
Figure 1: Peri-articular calcifications in the left hand.

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On April 2013, he was admitted in the intensive care department because of septic shock and acute respiratory insufficiency. On physical examination, his temperature was 40°C, pulse 150 beats per minute, his blood pressure was 150/90 mm Hg, and his oxygen saturation was 90% on 2 L of oxygen by nasal cannula. Pulmonary examination revealed polypnea with a respiratory rate of 32 breaths per minute and diffuse crackles at both lung bases. The mobilization of the left elbow was limited and painful. Neurological and cardiac examinations were unremarkable. The rest of the patient's examination was normal.

His arterial blood gas showed a mixed alkalosis with a pH of 7.48 (normal range, 7.38- 7.42), partial pressure of carbon dioxide of 35.5 mm Hg (normal range, 38-42 mm Hg), and partial pressure of oxygen of 126.3 mm Hg (normal range, 80-100 mm Hg) with HCO [3] of 27.1 mmol/L (normal range, 22-26 mmol/L) and a saturation of 98.2% under six liters of oxygen, lactates at 0.9 mmol/L (normal range, 0.33-1.1 mmol/L).

Laboratory evaluation revealed leukocytosis (white cell count: 22,200 cells/mm 3 ). No anemia or thrombocytopenia was noted, C-reactive protein 648 mg/L (normal range, 0-8 mg/L), procalcitonin >200 ng/mL (normal range <0.5 ng/mL), and the patient's liver function tests were normal. The results of cultures of removed HD catheter, stool, and urine were negatives. Transthoracic, transesophageal echocardiographies, and abdominal computed tomography (CT) scan were unremarkable. A coagulase negative staphylococcus was detected in three samples of blood culture.

Chest radiography showed right basal opacity [Figure 2]. CT pulmonary angiography showed all three arteries were calcified namely, the right pulmonary artery, the middle lobar artery, and the right upper lobar artery. The lumen of the right pulmonary artery showed emboli which were calcificated in periphery associated with a lower lobe alveolar consolidation along with ground glass opacities and right pleural effusion.
Figure 2: Chest radiography showing a systemized right basal opacity.

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Initially, the diagnosis of an HD catheterrelated sepsis with pulmonary localization was retained. The patient had been treated by broadspectrum antibiotics, but his dyspnea persisted although there was an improvement of the septic parameters. Pulmonary CT scan showed images evocating the diagnosis of metastatic pulmonary calcification (MPC) related to his malignant hyperparathyroidism (PTH: 1462 pg /mL). A bone scintigraphy performed using 15 mCi 99m Tc-methylene diphosphate was, therefore, done and revealed strikingly uniform and intense radioactivity accumulations in both lungs predominantly in the right lung. Increased radioactivity uptake was also observed in the elbows, shoulders, right hand, and pelvis.

A lung scintigraphy found a heterogeneous perfusion with participation in the global perfusion of 25% and 75%, respectively, of the right and left lung.

During his stay in the Intensive Care Unit, the course was marked by the occurrence of several infectious complications associated to frequent catheter thrombosis, thrombosis of the right subclavian, and the left iliac veins despite antithrombotic therapy at recommended therapeutic doses and a negative etiological investigations (protein S, C, antiphospholipid antibodies, antithrombin, V Leiden mutation, homocysteine, MTHFR mutation, antibody-associated nephritis, antineutrophil cytoplasmic antibodies, cryoglobulinemia, C3, C4, pathergy test, and HLA-B51).

The diagnosis of extraosseous calcification with uremic tumoral calcinosis, vascular and pulmonary calcification was finally made, the patient was anticoagulated with heparin and warfarin, while being maintained on Sevelamer ® along with intensive HD sessions with low calcium baths.

The outcome was favorable with the improvement of the respiratory status, the phosphocalcic parameters (calcium: 2.58 mmol/L, phosphorus: 2.34 mmol/L, PTH: 1078 pg/mL) and improvement of the radiological images on the chest X-rays.


   Discussion Top


Extraosseous calcification has plagued management of renal failure since the beginning of HD, but the issue has largely been neglected because the impact on survival was thought to be limited. [2] Calcification in patients with end-stage renal disease can produce a range of pathologies including calcific uremic arteriolopathy (formerly termed "calciphylaxis"), extraosseous soft tissue and solid organ calcification, corneal and conjunctival calcification, peritoneal calcification, and vascular and valvular calcification. [3]

Autopsy findings in the 1970s confirmed soft tissue, including vascular, calcification in 50- 80% of HD patients. [3] Data obtained in 120 uremic children between 1960 and 1983 revealed soft tissue calcification in 60%, most frequently involving blood vessels, lung, kidney, myocardium, central nervous system, and gastric mucosa. [4] Thus, extraosseous calcification is neither a new nor a dramatically increasing problem in uremic patients, but its high prevalence and prominent role in cardiovascular morbidity and mortality of uremic patients have only been recognized recently.

Calcium deposits occurred more frequently in the 1 st and 2 nd year of treatment. The factors responsible included the plasma calcium- phosphorus product, nonoptimal calcium, and magnesium ion concentration in the dialysis bath, and secondary hyperparathyroidism. [5] Systemic and local factors potentially involved in soft tissues calcifications in uremic patients are listed in [Table 1]. [6]
Table 1: Systemic and local factors involved in soft tissues calcifications in uremic patients.

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Various factors decrease the rate of calcification or even reverse established calcifications including PTH-related peptide, osteoprotegerin, bone morphogenic protein-7, and osteopontin, inorganic pyrophos phate, matrix GLA protein, and fetuin A. [3],[7]

In cases of uremic tumor calcinosis (UTC), the prevalence ranges from 0.5% to 3% in dialysis patients and may be underestimated due to lack of symptoms in its early stage. [8] The most common sites are the elbows, hips, hands, and wrists. The metastatic calcifications in dialysis patients are typically multiple, painless, large, and can become symptomatic with nerve compression and impairment of joint mobility [9] such as the case of our patient. The calcium deposits are typically multiple, para-articular, labile, and have a fluid-viscous consistency. "Active" lesions, that is, calcification centers surrounded by mononuclear or multinuclear macrophages, osteoclast-like giant cells, fibroblasts, and chronic inflammatory elements, can be distinguished from "inactive" lesions, in which calcified material is surrounded by fibrous tissue. [10]

The lung is one of the primary sites of metastatic calcium deposition. In autopsy series, MPC has been showed in 60-80% of HD patients although it's rarely recognized during life. [11] Calcium salts are predominantly deposited in the alveolar walls, and to a lesser extent in bronchial wall, pulmonary arteries, and veins. [12] The degree of respiratory distress often does not correlate with the degree of macroscopic calcification. Patients with extensive calcification may be asymptomatic, whereas others with subtle calcification or normal chest radiographs may have a severe respiratory compromise, and in some cases, these calcifications can cause fulminant respiratory failure and early death. Symptoms include dyspnea and chronic, nonproductive cough. [13] In our case, dyspnea was considered initially as the consequence of infectious pneumonitis and/or pulmonary embolism, but its persistence after improving sepsis and heparin therapy pointed to the diagnosis for MPC.

Because chest radiograph is insensitive in depicting small amounts of calcification, it is frequently reported as normal. Pulmonary calcifications have been described as confluent or patchy airspace opacities simulating pulmonary edema or pneumonia on chest radiographs. They can also appear as a diffuse interstitial process or as discrete or confluent calcified nodules. [14]

High-resolution CT, with its excellent sensitivity in the detection of small amounts of calcification, is being increasingly used to diagnose MPC. Several CT patterns have been documented to date. The first pattern is multiple diffuse calcified nodules that are either distributed throughout the whole lung or show a predilection for the apices. The second pattern is diffuse or patchy areas of ground-glass opacity or consolidation. Finally, MPC may appear as a confluent high attenuation parenchymal consolidation in a predominantly lobar distribution, mimicking lobar pneumonia. Associated findings include calcification in the bronchial walls, myocardium, and within the vessels of the chest wall. [14] Our case showed multiple, bilateral calcified nodules and patchy areas of ground-glass opacity throughout both lungs. In addition, this case also showed endoluminal calcification of the pulmonary veins.

The other useful technique in detecting early MPC is radionuclide imaging. Technetium99m-labeled bone scanning radionuclides detect pulmonary calcification. In addition, 99mTc bone scintigraphy with single-photon emission computed tomography may allow detection and localization of abnormality to the pulmonary parenchyma before abnormality is detected on chest radiography. [13]

Established calcifications are difficult to treat. Many therapeutic approaches were proposed in cases of extraosseous calcifications. In individual cases, marked clinical improvement and regression of extraosseous calcification have followed an increase in the dialysis dose, parathyroidectomy, and optimization of the calcium phosphate product, therapy with a bisphosphonate, therapy of aluminum overload, the use of phosphate binders, or successful renal transplantation. A single center study also noted a slower progression or even regression of peripheral arterial calcifications, as detected on plain radiographs, in end-stage renal disease patients with high serum magnesium levels. [3]

Calcium-free phosphate binding agents, such as Sevelamer ® , proposed by Chertow et al, suppresses ectopic calcifications in uremic rats. In a clinical study, Sevelamer ® slowed the progression of calcifications in coronary arteries and in the aorta although whether these effects relate to Sevelamer's phosphate-binding or lipid-lowering properties remains unclear. [15]

In case of UTC, large symptomatic tumoral calcinosis occasionally requires surgical intervention.

In our patient, Sevelamer ® with strict adherences to low calcium and phosphate regimen and regular HD were of benefit.


   Conclusion Top


Soft tissue calcification is a serious and frequent complication of chronic HD therapy. In particular, metastatic calcification may be life-threatening, especially when it involves the major organs. Our case illustrates the association between vascular, visceral, and periarticular calcifications due to poor calcium and phosphate control in an adolescent undisciplined HD patient.

Conflict of interest: None declared.

 
   References Top

1.
Alfrey AC, Solomons CC, Ciricillo J, Miller NL. Extraosseous calcification. Evidence for abnormal pyrophosphate metabolism in uremia. J Clin Invest 1976;57:692-9.  Back to cited text no. 1
    
2.
Ketteler M, Gross ML, Ritz E. Calcification and cardiovascular problems in renal failure. Kidney Int Suppl 2005;94:S120-7.  Back to cited text no. 2
    
3.
Floege J. When man turns to stone: Extraosseous calcification in uremic patients. Kidney Int 2004;65:2447-62.  Back to cited text no. 3
    
4.
Milliner DS, Zinsmeister AR, Lieberman E, Landing B. Soft tissue calcification in pediatric patients with end-stage renal disease. Kidney Int 1990;38:931-6.  Back to cited text no. 4
    
5.
Fabbri L, Fusaroli M, Catizone L, Zucchelli P. Periaticular metastatic calcifications in uremic patients. Minerva Med 1975;66:209-19.  Back to cited text no. 5
    
6.
Driieke TB. A clinical approach to the uraemic patient with extraskeletal calcifications. Nephrol Dial Transplant 1996;(11):37-42.  Back to cited text no. 6
    
7.
Efstratiadis G, Koskinas K, Pagourelias E. Coronary calcification in patients with end-stage renal disease: A novel endocrine disorder? Hormones (Athens) 2007;6:120-31.  Back to cited text no. 7
    
8.
Chang CC, Sung CC, Hsia CC, Lin SH. Uremic tumoral calcinosis causing atlantoaxial subluxation and spinal cord compression in a patient on continuous ambulatory peritoneal dialysis. Int Urol Nephrol 2013;45:1511-6.  Back to cited text no. 8
    
9.
Cofan F, García S, Combalia A, Campistol JM, Oppenheimer F, Ramón R. Uremic tumoral calcinosis in patients receiving longterm hemodialysis therapy. J Rheumatol 1999;26:379-85.  Back to cited text no. 9
    
10.
Steinbach LS, Johnston JO, Tepper EF, Honda GD, Martel W. Tumoral calcinosis: Radiologicpathologic correlation. Skeletal Radiol 1995;24: 573-8.  Back to cited text no. 10
    
11.
Sanders C, Frank MS, Rostand SG, Rutsky EA, Barnes GT, Fraser RG. Metastatic calcification of the heart and lungs in end-stage renal disease: Detection and quantification by dual-energy digital chest radiography. AJR Am J Roentgenol 1987;149:881-7.  Back to cited text no. 11
    
12.
Bein ME, Lee DB, Mink JH, Dickmeyer J. Unusual case of metastatic pulmonary calcification. AJR Am J Roentgenol 1979;132: 812-6.  Back to cited text no. 12
    
13.
Brodeur FJ Jr., Kazerooni EA. Metastatic pulmonary calcification mimicking air-space disease. Technetium-99m-MDP SPECT imaging. Chest 1994;106:620-2.  Back to cited text no. 13
    
14.
Hartman TE, Müller NL, Primack SL, et al. Metastatic pulmonary calcification in patients with hypercalcemia: Findings on chest radiographs and CT scans. AJR Am J Roentgenol 1994;162:799-802.  Back to cited text no. 14
    
15.
Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002;62:2  Back to cited text no. 15
    

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Correspondence Address:
Jannet Labidi
Department of Internal Medicine, Military Hospital, 1008 Mont Fleury, Tunis
Tunisia
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DOI: 10.4103/1319-2442.190884

PMID: 27752018

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