Thoracic Complications in Chronic Kidney Disease-Clinical and ...


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  • Bat wing edema refers to a central, nongravitational distribution of alveolar edema. It is seen in less than 10% of cases of pulmonary edema ( 4 ) and generally occurs with rapidly developing severe cardiac failure as seen in acute mitral insufficiency (associated with papillary muscle rupture, massive myocardial infarct, and valve leaflet destruction due to septic endocarditis) or renal failure ( Figs 3 , 4 ). In bat wing edema, the lung cortex is free of alveolar or interstitial fluid. This pathologic condition develops so rapidly that it is initially observed as an alveolar infiltrate, and the preceding interstitial phase that is typically seen in pulmonary edema goes undetected radiologicallySeveral theories have been proposed to explain the pathophysiology of bat wing edema. One such theory involves an increase in hydraulic conductivity. Mucopolysaccharides fill the spaces in the perivascular cytoskeleton and, under normal conditions, inhibit the flow of liquid. However, with increased tissue hydration, this extracellular matrix allows water to easily flow centrally ( 4 ). Other investigators have suggested a pumping effect of the respiratory cycle, which is more pronounced in the lung cortex ( 10 ) and causes overall fluid flow toward the hilum. Another probable contributing factor is the contractile property of alveolar septa, which allows them to expel interstitial edema toward the hilum ( 4 ).
  • Thoracic Complications in Chronic Kidney Disease-Clinical and ...

    1. 1. Clinical and Radiographic Findings in a Patient With Chronic Kidney Disease Erica Boettcher Radiology Elective November 2005
    2. 2. Case Presentation: Mr. B <ul><li>HPI: </li></ul><ul><ul><li>47 yr-old man with Chronic Kidney Disease presents with 3-months of nonproductive cough </li></ul></ul><ul><ul><li>Also complains of mild breathlessness on exertion; otherwise feels well </li></ul></ul><ul><ul><li>Denies fevers/chills/weight loss/hemoptysis </li></ul></ul><ul><ul><li>No s/o sinus disease, asthma, GERD </li></ul></ul><ul><ul><li>PPD non-reactive </li></ul></ul>Janssen WJ, Sippel JM. Persistent Radiographic Infiltrates in a Patient with Chronic Cough. Chest 2005; 128: 1879-1881.
    3. 3. Case: Mr. B con’t <ul><li>PMH: </li></ul><ul><ul><li>Chronic Kidney Disease </li></ul></ul><ul><ul><ul><li>2/2 HTN </li></ul></ul></ul><ul><ul><ul><li>Hemodialysis dependent x 4 years </li></ul></ul></ul><ul><li>Meds : minoxidil, labetalol, and calcium acetate </li></ul><ul><li>SH: </li></ul><ul><ul><li>Retired construction worker </li></ul></ul><ul><ul><li>Denies tobacco/alcohol/illicit drugs </li></ul></ul><ul><ul><li>No recent travel </li></ul></ul>
    4. 4. Case: Mr. B con’t <ul><li>PE: </li></ul><ul><ul><li>O2 sat 94% </li></ul></ul><ul><ul><li>No JVD </li></ul></ul><ul><ul><li>No lymphadenopathy </li></ul></ul><ul><ul><li>Lungs clear </li></ul></ul><ul><ul><li>CV exam normal </li></ul></ul><ul><ul><li>No peripheral edema </li></ul></ul><ul><li>Labs: serum Ca 9.5, phos 5.2, Hct 44% </li></ul>
    5. 5. Case: Mr. B con’t <ul><li>CXR reveals patchy areas of consolidative opacities bilaterally </li></ul>Janssen WJ, ibid
    6. 6. Case: Mr. B con’t <ul><li>CT findings demonstrate R>L consolidative opacities </li></ul>Janssen WJ, ibid
    7. 7. Case: Mr. B con’t <ul><li>What is the most likely diagnosis? </li></ul>
    8. 8. Case: Mr. B con’t <ul><li>Answer: Metastatic calcification secondary to chronic kidney disease </li></ul>
    9. 9. Case: Mr. B con’t <ul><li>Question #1: How does Chronic Kidney Disease cause calcification in the lungs? </li></ul><ul><li>Question #2: Why is this important? </li></ul>
    10. 10. Outline <ul><li>Introduction- Chronic Kidney Disease (CKD) </li></ul><ul><li>Metastatic pulmonary </li></ul><ul><ul><li>calcification </li></ul></ul><ul><li>Other common thoracic manifestations of CKD that can mimic metastatic </li></ul><ul><li>calcification </li></ul><ul><ul><li>Bronchopulmonary infections </li></ul></ul><ul><ul><li>Pulmonary Edema </li></ul></ul><ul><li>Summary </li></ul>
    11. 11. Chronic Kidney Disease <ul><li>Magnitude of the disease: </li></ul><ul><ul><li>Over the past several years there has been continued growth of the total number of CKD patients requiring dialysis </li></ul></ul><ul><ul><li>Since 1988 the prevalent dialysis population has tripled </li></ul></ul><ul><ul><li>Medicare costs for End Stage Renal Disease rose to $18.1 billion in 2003 (3 times the costs incurred in 1991) and represented 6.6% of total Medicare expenditures </li></ul></ul><ul><li>By the end of 2003 there were 453,000 patients receiving treatment for ESRD: </li></ul><ul><ul><li>325,000 patients on dialysis </li></ul></ul><ul><ul><li>128,000 transplant patients </li></ul></ul><ul><li>Ongoing progress of hemodialysis/peritoneal dialysis and renal transplant have improved prognosis in kidney disease </li></ul>Renal Data System. USRDS 2005 Annual Data Report: Atlas of ESRD in the United States. Bethesda, Md: National Institutes of Health, National Institute of Diabetes Mellitus and Digestive and Kidney Diseases, 2005.
    12. 12. Metastatic Calcification-what is it? <ul><li>Calcification=deposition of calcium salts in soft tissues </li></ul><ul><li>Organs most commonly affected: stomach, kidneys, lungs, heart, and blood vessels </li></ul><ul><li>Lungs are particularly susceptible </li></ul><ul><li>Metastatic calcification: </li></ul><ul><ul><li>calcium deposits in normal tissues </li></ul></ul><ul><li>Dystrophic calcification : </li></ul><ul><ul><li>calcium deposits in previously damaged tissue </li></ul></ul><ul><ul><li>seen in: </li></ul></ul><ul><ul><ul><li>granulomatous disorders such as tuberculosis, histoplasmosis, coccidiomycosis, and sarcoidosis </li></ul></ul></ul><ul><ul><ul><li>following infection such as pneumocystis and varicella </li></ul></ul></ul><ul><ul><ul><li>with occupational lung diseases including silicosis and coal worker’s pneumoconiosis </li></ul></ul></ul>
    13. 13. Metastatic Calcification-causes? <ul><li>Metastatic calcification is further divided into benign and malignant causes </li></ul><ul><li>Benign Causes: </li></ul><ul><ul><li>By far the most common: patients on hemodialysis for chronic kidney disease </li></ul></ul><ul><ul><li>60-75% of chronic dialysis patients have some degree of pulmonary calcification at autopsy </li></ul></ul><ul><ul><li>Other benign causes (rare): orthotopic liver transplantation, primary hyperparathyroidism, milk-alkali syndrome, hypervitaminosis D, osteopetrosis, Paget’s disease </li></ul></ul>Janssen WJ, ibid
    14. 14. Proposed Mechanisms of Metastatic Lung Calcification <ul><li>Pathogenesis is poorly understood </li></ul><ul><li>No single factor is responsible </li></ul><ul><li>Possible contributing factors: </li></ul><ul><ul><li>Elevated serum phosphorus and calcium levels (common in CKD, but levels correlate poorly with development of pulmonary calcification) </li></ul></ul><ul><ul><li>Alkaline pH which favors precipitation of calcium phosphate in tissues ( intermittent alkalosis follows bicarb hemodialysis) </li></ul></ul><ul><ul><li>Parathyroid hormone ( removal of parathyroid glands from laboratory animals with CKD prevents pulmonary calcinosis) </li></ul></ul>Chan ED, Morales DV, Welsh CH, McDermott MT, and Schwarz MI. Calcium deposition with or without bone formation in the lung. Am J Respir Crit Care Med 2002, 165: 1654-1669.
    15. 15. Histology of Metastatic Lung Calcification <ul><li>Histology: </li></ul><ul><ul><li>Linear calcific deposits in alveolar septal walls with secondary fibroproliferative response </li></ul></ul><ul><ul><li>Calcification of the elastic lamina in small and medium-sized pulmonary vessels and within bronchial basement membrane </li></ul></ul>Chan, ibid
    16. 16. Metastatic Calcification: CXR <ul><li>While chest radiographs are useful for detection of pleural calcification, hilar-mediastinal lymph node calcification, and calcified lung nodules, they are less sensitive for parenchymal calcification </li></ul><ul><li>For parenchymal calcification, CXR can reveal any of the following patterns: </li></ul><ul><ul><li>Diffuse ground glass/reticular opacities, stable in time or slowly progressive (heart size and pulmonary vasculature normal) </li></ul></ul><ul><ul><li>Low-density apical opacities </li></ul></ul><ul><ul><li>Calcified nodules </li></ul></ul>Gavelli, ibid
    17. 17. Metastatic Calcification: CXR <ul><li>CXR are unable to detect small amounts of calcium </li></ul><ul><li>When compared with autopsy results, CXR demonstrate parenchymal calcification in <15% of patients </li></ul><ul><li>In cases where CXR are abnormal, findings are nonspecific and may be mistaken for pulmonary edema or pneumonia, both of which are common manifestations of CKD </li></ul><ul><li>Abnormalities can also be mistaken for hemorrhage, infarct, or malignancy </li></ul><ul><ul><li>Lingam RK, et al. Metastatic pulmonary calcifications in renal failure: a new HRCT pattern. Brit Jour Rad 2002, 75: 74-77. </li></ul></ul>
    18. 18. Metastatic Calcification: Helpful Imaging <ul><li>Preferred imaging: </li></ul><ul><ul><li>High-resolution computer tomography (HRCT) scan </li></ul></ul><ul><ul><li>99m technetium-methylene diphosphate bone scintigraphy </li></ul></ul><ul><ul><li>These modalities are more sensitive and specific than CXR for detection of pulmonary calcification </li></ul></ul><ul><li>Main use for imaging: early recognition of lung calcification in at-risk individuals to identify unexplained chronic areas of opacification (thereby avoiding surgical lung biopsy) </li></ul>
    19. 19. Metastatic Calcification: CT <ul><li>Standard 7- or 10-mm-thick images may fail to detect microscopic calcification due to signal averaging from normal adjacent tissue, therefore HRCT is preferred </li></ul><ul><li>HRCT is relatively specific for pulmonary calcification </li></ul><ul><li>Caveat: presence of dense lesions on lung window images will not distinguish between noncalcified and calcified opacities </li></ul>Hartman TE, Muller N, Primack SL, Johkoh T, Takeuchi N, et al. Metastatic pulmonary calcification in patients with hypercalcaemia: findings on chest radiographs and CT scans. AJR 1994;162:799–802.
    20. 20. Metastatic Calcification: CT con’t <ul><li>Patterns seen on HRCT scan: </li></ul><ul><li>diffuse or patchy ground-glass opacification </li></ul><ul><li>dense consolidation, often in a lobar distribution, and </li></ul><ul><li>multiple nodules in a diffuse or localized distribution </li></ul><ul><li>These patterns are not mutually exclusive, and a combination of the different patterns may exist </li></ul>Chan, ibid
    21. 21. Imaging: 99m Tc-MDP Bone Scintigraphy <ul><li>Alternative to HRCT: Bone Scintigraphy </li></ul><ul><li>Highly specific for pulmonary calcification </li></ul><ul><li>Useful to sort out equivocal cases on HRCT (calcified vs noncalcified opacities) </li></ul>Bone scintigraphy of a patient with metastatic calcification due to CRF and on hemodialysis. Note the increased uptake of 99mTc-MDP calcium-avid radiotracer in both lungs (right greater than left)and the stomach. Chan, ibid
    22. 22. Clinical Significance of Metastatic Calcification <ul><li>By some reports, ~90% of patients with CKD have abnormal pulmonary function test results </li></ul><ul><li>Most common abnormality is: </li></ul><ul><ul><li>impaired diffusion capacity (decrease in DLCO) </li></ul></ul><ul><li>Pulmonary calcification may contribute to these abnormalities by increasing vascular permeability and inducing interstitial fibrosis </li></ul><ul><li>In some studies, tissue calcium content from biopsy specimens correlates strongly with reductions in PaO2, vital capacity, and diffusion </li></ul>Bush A, Gabriel R. Pulmonary function in chronic renal failure: effects of dialysis and transplantation. Thorax 1991; 46: 424-28.
    23. 23. Clinical Significance of Metastatic Calcification con’t <ul><li>There are little data regarding the natural history of metastatic pulmonary calcification </li></ul><ul><li>Majority of patients are asymptomatic but can present with dyspnea and cough </li></ul><ul><li>Most often process is slowly progressive but pulmonary fibrosis, cor pulmonale, and respiratory failure develops in a minority of patients </li></ul>Janssen, ibid
    24. 24. Clinical Significance of Metastatic Calcification con’t <ul><li>Therapeutic options are limited: </li></ul><ul><ul><li>Therapy is aimed at correcting hypercalcemia and hyperphosphatemia </li></ul></ul><ul><li>Renal transplantation may lead to disease remission in some patients, while in others, the disease may progress despite normal functioning allograft </li></ul>Hartman, ibid
    25. 25. Clinical Significance of Metastatic Calcification con’t <ul><li>Take home point: remember to consider metastatic calcification when working up a patient with Chronic Kidney Disease and an abnormal chest radiograph! </li></ul>
    26. 26. Other Common Thoracic Complications of CKD <ul><li>Bronchopulmonary infections and Pulmonary Edema </li></ul><ul><li>These can be indistinguishable from metastatic calcification on CXR </li></ul>
    27. 27. Bronchopulmonary infections <ul><li>Infection is frequent cause of morbidity and mortality among patients with CKD and ESRD receiving dialysis </li></ul><ul><li>In 2001 Sarnak and colleagues obtained data from 50,227 deaths from ESRD (years 1994-1996) and 2.27 million deaths from general population (year 1993) </li></ul><ul><li>Found that pulmonary infectious mortality is ~10-fold higher in dialysis patients compared to general population, despite stratification for age </li></ul>Sarnak MJ and Jaber BL. Pulmonary infectious mortality among patients with end-stage-renal-disease. Chest 2001; 120: 1883-87.
    28. 28. Bronchopulmonary infections con’t <ul><li>Typical presentation of infection on CXR: </li></ul><ul><ul><li>Nodular lesions and/or consolidation, either patchy or diffuse </li></ul></ul><ul><li>Typical infections: </li></ul><ul><ul><li>Staphylococcal pneumonia </li></ul></ul><ul><ul><li>Septic embolism </li></ul></ul><ul><ul><li>Tuberculosis/Fungal </li></ul></ul><ul><ul><li>Streptococcal pneumonia </li></ul></ul>Coskun M, Boyvat F, Bozkurt B, Agildere A, and Niron E. Thoracic CT findings in long-term hemodialysis patients. Acta Radiologica 1999; 40: 181-86.
    29. 29. Bronchopulmonary infections con’t <ul><li>Potential reasons why dialysis patients may be particularly susceptible to pulmonary infections: </li></ul><ul><ul><li>Pulmonary functional abnormalities </li></ul></ul><ul><ul><li>Depressed cellular and humoral immunity </li></ul></ul><ul><ul><li>Impaired phagocytic cell function </li></ul></ul>Sarnak, ibid
    30. 30. Pulmonary Edema in CKD <ul><li>Pulmonary edema can occur secondary to many interacting factors in CKD, but pathogenesis appears largely based on hemodynamics </li></ul>
    31. 31. Pulmonary Edema in CKD con’t <ul><li>According to Milne colleagues it is possible to distinguish, on CXR, cardiogenic from renal edema </li></ul><ul><ul><li>Typical pattern of “renal” edema: “bat-wing” distribution </li></ul></ul><ul><ul><li>Translation: central, nongravitational distribution of edema </li></ul></ul>Milne E, Pistolesi M, Miniati M, Guintini C. The radiologic distinction of cardiogenic and noncardiogenic pulmonary edema. AJR 1985, 144:879-94
    32. 32. Pulmonary Edema in CKD con’t . Gluecker T, et al. Clinical and radiologic features of pulmonary edema. Radiographics 1999; 19: 1507-31 “ Bat-wing” distribution
    33. 33. Pulmonary Edema in CKD con’t <ul><li>Caveats for “renal” edema in “bat-wing” distribution: </li></ul><ul><ul><li>“ Bat-wing” pattern is not specific to renal failure: </li></ul></ul><ul><ul><ul><li>It can occur with rapidly developing severe cardiac failure as seen in acute mitral insufficiency (associated with papillary muscle rupture, massive myocardial infarct, and valve leaflet destruction due to septic endocarditis) </li></ul></ul></ul><ul><ul><li>Not all “renal” edemas present with “bat-wing” distribution </li></ul></ul><ul><ul><ul><li>Experimental and clinical studies with CT, performed during pulmonary edema of various origins, have demonstrated a large variety of distribution for the pulmonary opacities </li></ul></ul></ul>Gavelli, ibid
    34. 34. Summary <ul><li>Chronic Kidney Disease is a relatively common disease in the US </li></ul><ul><li>One common thoracic manifestation of CKD is pulmonary metastatic calcification </li></ul><ul><li>Little is known about the pathogenesis or natural history of metastatic calcification </li></ul><ul><li>It is important to consider pulmonary calcification when working up a patient with CKD and an abnormal CXR </li></ul><ul><li>Metastatic calcification can be mistaken for other common thoracic manifestations of CKD, including bronchopulmonary infection or pulmonary edema </li></ul><ul><li>HRCT and 99m Tc-MDP Bone Scintigraphy can be used to differentiate pulmonary calcification from other disease processes </li></ul>