CKD Pulmonary

Clinical and Radiographic Clinical and Radiographic Findings in a Patient With Findings in a Patient With Chronic Kidney DiseaseChronic Kidney DiseaseErica Boettcher Erica Boettcher

Radiology ElectiveRadiology Elective

November 2005November 2005

Case Presentation: Mr. BCase Presentation: Mr. B

HPI:HPI: 47 yr-old man with Chronic Kidney Disease 47 yr-old man with Chronic Kidney Disease

presents with 3-months of nonproductive presents with 3-months of nonproductive coughcough

Also complains of mild breathlessness on Also complains of mild breathlessness on exertion; otherwise feels wellexertion; otherwise feels well

Denies fevers/chills/weight loss/hemoptysisDenies fevers/chills/weight loss/hemoptysis No s/o sinus disease, asthma, GERDNo s/o sinus disease, asthma, GERD PPD non-reactivePPD non-reactive

Janssen WJ, Sippel JM. Persistent Radiographic Infiltrates in a Patient with Chronic Cough. Chest 2005; 128: 1879-1881.

Case: Mr. B con’tCase: Mr. B con’t

PMH:PMH: Chronic Kidney Disease Chronic Kidney Disease

• 2/2 HTN2/2 HTN• Hemodialysis dependent x 4 yearsHemodialysis dependent x 4 years

MedsMeds: minoxidil, labetalol, and calcium acetate: minoxidil, labetalol, and calcium acetate SH:SH:

Retired construction workerRetired construction worker Denies tobacco/alcohol/illicit drugsDenies tobacco/alcohol/illicit drugs No recent travelNo recent travel


PE:PE: O2 sat 94%O2 sat 94% No JVDNo JVD No lymphadenopathyNo lymphadenopathy Lungs clearLungs clear CV exam normalCV exam normal No peripheral edemaNo peripheral edema

Labs:Labs: serum Ca 9.5, phos 5.2, Hct 44% serum Ca 9.5, phos 5.2, Hct 44%

Case: Mr. B con’tCase: Mr. B con’t CXR reveals patchy areas of consolidative opacities bilaterallyCXR reveals patchy areas of consolidative opacities bilaterally

Janssen WJ, ibid


CT findings demonstrate R>L consolidative opacitiesCT findings demonstrate R>L consolidative opacities

Janssen WJ, ibid


What is the most likely diagnosis?What is the most likely diagnosis?


Answer: Metastatic calcification secondary Answer: Metastatic calcification secondary to chronic kidney diseaseto chronic kidney disease


Question #1: How does Chronic Kidney Question #1: How does Chronic Kidney Disease cause calcification in the lungs?Disease cause calcification in the lungs?

Question #2: Why is this important?Question #2: Why is this important?

OutlineOutline

Introduction- Chronic Kidney Disease (CKD)Introduction- Chronic Kidney Disease (CKD) Metastatic pulmonaryMetastatic pulmonary

calcificationcalcification Other common thoracic manifestations of CKD Other common thoracic manifestations of CKD

that can mimic metastatic that can mimic metastatic calcificationcalcification

Bronchopulmonary infectionsBronchopulmonary infections Pulmonary EdemaPulmonary Edema

SummarySummary

Chronic Kidney Disease Chronic Kidney Disease

Magnitude of the disease:Magnitude of the disease: Over the past several years there has been continued growth of Over the past several years there has been continued growth of

the total number of CKD patients requiring dialysisthe total number of CKD patients requiring dialysis Since 1988 the prevalent dialysis population has tripledSince 1988 the prevalent dialysis population has tripled Medicare costs for End Stage Renal Disease rose to $18.1 Medicare costs for End Stage Renal Disease rose to $18.1

billion in 2003 (3 times the costs incurred in 1991) and billion in 2003 (3 times the costs incurred in 1991) and represented 6.6% of total Medicare expendituresrepresented 6.6% of total Medicare expenditures

By the end of 2003 there were 453,000 patients By the end of 2003 there were 453,000 patients receiving treatment for ESRD:receiving treatment for ESRD:

325,000 patients on dialysis325,000 patients on dialysis 128,000 transplant patients 128,000 transplant patients

Ongoing progress of hemodialysis/peritoneal dialysis and Ongoing progress of hemodialysis/peritoneal dialysis and renal transplant have improved prognosis in kidney renal transplant have improved prognosis in kidney diseasedisease

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.

Metastatic Calcification-what is it?Metastatic Calcification-what is it?

Calcification=deposition of calcium salts in soft tissuesCalcification=deposition of calcium salts in soft tissues Organs most commonly affected: stomach, kidneys, lungs, Organs most commonly affected: stomach, kidneys, lungs,

heart, and blood vesselsheart, and blood vessels Lungs are particularly susceptibleLungs are particularly susceptible Metastatic calcification: Metastatic calcification:

calcium deposits in normal tissuescalcium deposits in normal tissues

Dystrophic calcificationDystrophic calcification:: calcium deposits in previously damaged tissuecalcium deposits in previously damaged tissue seen in:seen in:

• granulomatous disorders such as tuberculosis, histoplasmosis, granulomatous disorders such as tuberculosis, histoplasmosis, coccidiomycosis, and sarcoidosis coccidiomycosis, and sarcoidosis

• following infection such as pneumocystis and varicellafollowing infection such as pneumocystis and varicella• with occupational lung diseases including silicosis and coal worker’s with occupational lung diseases including silicosis and coal worker’s

pneumoconiosispneumoconiosis

Metastatic Calcification-causes?Metastatic Calcification-causes?

Metastatic calcification is further divided into Metastatic calcification is further divided into benign and malignant causesbenign and malignant causes

Benign Causes:Benign Causes: By far the most common:By far the most common: patients on hemodialysis patients on hemodialysis

for chronic kidney disease for chronic kidney disease 60-75% of chronic dialysis patients have some degree 60-75% of chronic dialysis patients have some degree

of pulmonary calcification at autopsyof pulmonary calcification at autopsy Other benign causes (rare):Other benign causes (rare): orthotopic liver orthotopic liver

transplantation, primary hyperparathyroidism, milk-transplantation, primary hyperparathyroidism, milk-alkali syndrome, hypervitaminosis D, osteopetrosis, alkali syndrome, hypervitaminosis D, osteopetrosis, Paget’s diseasePaget’s disease

Janssen WJ, ibid

Proposed Mechanisms of Proposed Mechanisms of Metastatic Lung CalcificationMetastatic Lung Calcification

Pathogenesis is poorly understoodPathogenesis is poorly understood No single factor is responsibleNo single factor is responsible Possible contributing factors: Possible contributing factors:

Elevated serum phosphorus and calcium levelsElevated serum phosphorus and calcium levels (common in (common in CKD, but levels correlate poorly with development of pulmonary CKD, but levels correlate poorly with development of pulmonary calcification)calcification)

Alkaline pH which favors precipitation of calcium phosphate Alkaline pH which favors precipitation of calcium phosphate in tissues (in tissues (intermittent alkalosis follows bicarb hemodialysis)intermittent alkalosis follows bicarb hemodialysis)

Parathyroid hormone (Parathyroid hormone (removal of parathyroid glands from removal of parathyroid glands from laboratory animals with CKD prevents pulmonary calcinosis)laboratory animals with CKD prevents pulmonary calcinosis)

Chan ED, Morales DV, Welsh CH, McDermott MT, and Schwarz MI. 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 Calcium deposition with or without bone formation in the lung. Am J Respir Crit Care Med 2002, 165: 1654-1669.Care Med 2002, 165: 1654-1669.

Histology of Metastatic Lung Histology of Metastatic Lung CalcificationCalcification

Histology:Histology: Linear calcific deposits in alveolar septal walls with secondary Linear calcific deposits in alveolar septal walls with secondary

fibroproliferative responsefibroproliferative response Calcification of the elastic lamina in small and medium-sized Calcification of the elastic lamina in small and medium-sized

pulmonary vessels and within bronchial basement membranepulmonary vessels and within bronchial basement membrane

Chan, ibid

Metastatic Calcification: CXRMetastatic Calcification: CXR

While chest radiographs are useful for detection of While chest radiographs are useful for detection of pleural calcification, hilar-mediastinal lymph node pleural calcification, hilar-mediastinal lymph node calcification, and calcified lung nodules, they are less calcification, and calcified lung nodules, they are less sensitive for parenchymal calcificationsensitive for parenchymal calcification

For parenchymal calcification, CXR can reveal any of For parenchymal calcification, CXR can reveal any of the following patterns:the following patterns:

Diffuse ground glass/reticular opacities, stable in time or Diffuse ground glass/reticular opacities, stable in time or slowly progressive (heart size and pulmonary vasculature slowly progressive (heart size and pulmonary vasculature normal)normal)

Low-density apical opacitiesLow-density apical opacities Calcified nodulesCalcified nodules

Gavelli, ibid

Metastatic Calcification: CXRMetastatic Calcification: CXR CXR are unable to detect small amounts of CXR are unable to detect small amounts of

calciumcalcium When compared with autopsy results, CXR When compared with autopsy results, CXR

demonstrate parenchymal calcification in <15% demonstrate parenchymal calcification in <15% of patientsof patients

In cases where CXR are abnormal, findings are In cases where CXR are abnormal, findings are nonspecific and may be mistaken for pulmonary nonspecific and may be mistaken for pulmonary edema or pneumonia, both of which are edema or pneumonia, both of which are common manifestations of CKDcommon manifestations of CKD

Abnormalities can also be mistaken for Abnormalities can also be mistaken for hemorrhage, infarct, or malignancyhemorrhage, infarct, or malignancy

Lingam RK, et al. Metastatic pulmonary calcifications in renal failure: a new HRCT pattern. Brit Jour Rad 2002, 75: 74-77.Lingam RK, et al. Metastatic pulmonary calcifications in renal failure: a new HRCT pattern. Brit Jour Rad 2002, 75: 74-77.

Metastatic Calcification: Helpful Metastatic Calcification: Helpful Imaging Imaging

Preferred imaging: Preferred imaging: High-resolution computer tomography (HRCT) scan High-resolution computer tomography (HRCT) scan 99m99mtechnetium-methylene diphosphate bone technetium-methylene diphosphate bone

scintigraphyscintigraphy These modalities are more sensitive and specific than These modalities are more sensitive and specific than

CXR for detection of pulmonary calcificationCXR for detection of pulmonary calcification

Main use for imaging: early recognition of lung Main use for imaging: early recognition of lung calcification in at-risk individuals to identify calcification in at-risk individuals to identify unexplained chronic areas of opacification unexplained chronic areas of opacification (thereby avoiding surgical lung biopsy)(thereby avoiding surgical lung biopsy)

Metastatic Calcification: CTMetastatic Calcification: CT

Standard 7- or 10-mm-thick images may fail to Standard 7- or 10-mm-thick images may fail to detect microscopic calcification due to signal detect microscopic calcification due to signal averaging from normal adjacent tissue, averaging from normal adjacent tissue, therefore HRCT is preferred therefore HRCT is preferred

HRCT is relatively specific for pulmonary HRCT is relatively specific for pulmonary calcificationcalcification

Caveat: presence of dense lesions on lung Caveat: presence of dense lesions on lung window images will not distinguish between window images will not distinguish between noncalcified and calcified opacities noncalcified and calcified opacities

Hartman TE, Muller N, Primack SL, Johkoh T, Takeuchi N, et al. Metastatic pulmonary calcification in patients with hypercalcaemia: findings on chest 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.radiographs and CT scans. AJR 1994;162:799–802.

Metastatic Calcification: CT con’tMetastatic Calcification: CT con’t

Patterns seen on HRCT scan: Patterns seen on HRCT scan: (1)(1) diffuse or patchy ground-glass opacificationdiffuse or patchy ground-glass opacification(2)(2) dense consolidation, often in a lobar distribution, and dense consolidation, often in a lobar distribution, and (3)(3) multiple nodules in a diffuse or localized distributionmultiple nodules in a diffuse or localized distribution These patterns are not mutually exclusive, and a combination of the These patterns are not mutually exclusive, and a combination of the

different patterns may existdifferent patterns may exist

Chan, ibid

Imaging: Imaging: 99m99mTc-MDP Bone Tc-MDP Bone ScintigraphyScintigraphy

Alternative to HRCT: Bone Alternative to HRCT: Bone ScintigraphyScintigraphy

Highly specific for pulmonary Highly specific for pulmonary calcificationcalcification

Useful to sort out equivocal Useful to sort out equivocal cases on HRCT (calcified vs cases on HRCT (calcified vs noncalcified opacities)noncalcified opacities) Bone scintigraphy of a patient with Bone scintigraphy of a patient with

metastatic calcification due to CRF metastatic calcification due to CRF and on hemodialysis. Note theand on hemodialysis. Note the increased uptake of 99mTc-MDPincreased uptake of 99mTc-MDPcalcium-avid radiotracer in both calcium-avid radiotracer in both lungs (right greater than left)and the lungs (right greater than left)and the stomach. stomach.

Chan, ibid

Clinical Significance of Metastatic Clinical Significance of Metastatic CalcificationCalcification

By some reports, ~90% of patients with CKD By some reports, ~90% of patients with CKD have abnormal pulmonary function test resultshave abnormal pulmonary function test results

Most common abnormality is:Most common abnormality is: impaired diffusion capacity (decrease in DLCO)impaired diffusion capacity (decrease in DLCO)

Pulmonary calcification may contribute to these Pulmonary calcification may contribute to these abnormalities by increasing vascular abnormalities by increasing vascular permeability and inducing interstitial fibrosispermeability and inducing interstitial fibrosis

In some studies, tissue calcium content from In some studies, tissue calcium content from biopsy specimens correlates strongly with biopsy specimens correlates strongly with reductions in PaO2, vital capacity, and diffusionreductions in PaO2, vital capacity, and diffusion

Bush A, Gabriel R. Pulmonary function in chronic renal failure: effects of dialysis and transplantation. Thorax 1991; 46: 424-28.

Clinical Significance of Metastatic Clinical Significance of Metastatic Calcification con’tCalcification con’t

There are little data regarding the natural history There are little data regarding the natural history of metastatic pulmonary calcificationof metastatic pulmonary calcification

Majority of patients are asymptomatic but can Majority of patients are asymptomatic but can present with dyspnea and coughpresent with dyspnea and cough

Most often process is slowly progressive but Most often process is slowly progressive but pulmonary fibrosis, cor pulmonale, and pulmonary fibrosis, cor pulmonale, and respiratory failure develops in a minority of respiratory failure develops in a minority of patientspatients

Janssen, ibid


Therapeutic options are limited:Therapeutic options are limited: Therapy is aimed at correcting hypercalcemia Therapy is aimed at correcting hypercalcemia

and hyperphosphatemia and hyperphosphatemia Renal transplantation may lead to disease Renal transplantation may lead to disease

remission in some patients, while in remission in some patients, while in others, the disease may progress despite others, the disease may progress despite normal functioning allograftnormal functioning allograft

Hartman, ibid


Take home point: remember to consider Take home point: remember to consider metastatic calcification when working up a metastatic calcification when working up a patient with Chronic Kidney Disease and patient with Chronic Kidney Disease and an abnormal chest radiograph! an abnormal chest radiograph!

Other Common Thoracic Other Common Thoracic Complications of CKDComplications of CKD

Bronchopulmonary infections Bronchopulmonary infections and and Pulmonary EdemaPulmonary Edema

These can be indistinguishable from These can be indistinguishable from metastatic calcification on CXRmetastatic calcification on CXR

Bronchopulmonary infectionsBronchopulmonary infections

Infection is frequent cause of morbidity and Infection is frequent cause of morbidity and mortality among patients with CKD and ESRD mortality among patients with CKD and ESRD receiving dialysisreceiving dialysis

In 2001 Sarnak and colleagues obtained data In 2001 Sarnak and colleagues obtained data from 50,227 deaths from ESRD (years 1994-from 50,227 deaths from ESRD (years 1994-1996) and 2.27 million deaths from general 1996) and 2.27 million deaths from general population (year 1993) population (year 1993)

Found that pulmonary infectious mortality is ~10-Found that pulmonary infectious mortality is ~10-fold higher in dialysis patients compared to fold higher in dialysis patients compared to general population, despite stratification for agegeneral population, despite stratification for age

Sarnak MJ and Jaber BL. Pulmonary infectious mortality among patients with end-stage-renal-disease. Chest 2001; 120: 1883-87.

Bronchopulmonary infections con’tBronchopulmonary infections con’t

Typical presentation of infection on CXR:Typical presentation of infection on CXR: Nodular lesions and/or consolidation, either Nodular lesions and/or consolidation, either

patchy or diffusepatchy or diffuse Typical infections:Typical infections:

Staphylococcal pneumoniaStaphylococcal pneumonia Septic embolismSeptic embolism Tuberculosis/FungalTuberculosis/Fungal Streptococcal pneumoniaStreptococcal pneumonia

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.

Bronchopulmonary infections con’tBronchopulmonary infections con’t

Potential reasons why dialysis patients Potential reasons why dialysis patients may be particularly susceptible to may be particularly susceptible to pulmonary infections:pulmonary infections: Pulmonary functional abnormalitiesPulmonary functional abnormalities Depressed cellular and humoral immunityDepressed cellular and humoral immunity Impaired phagocytic cell functionImpaired phagocytic cell function

Sarnak, ibid

Pulmonary Edema in CKDPulmonary Edema in CKD

Pulmonary edema can occur secondary Pulmonary edema can occur secondary to many interacting factors in CKD, but to many interacting factors in CKD, but pathogenesis appears largely based on pathogenesis appears largely based on hemodynamicshemodynamics

Pulmonary Pulmonary Edema in CKD con’tEdema in CKD con’t

According to Milne colleagues it is According to Milne colleagues it is possible to distinguish, on CXR, possible to distinguish, on CXR, cardiogenic from renal edemacardiogenic from renal edema Typical pattern of “renal” edema: “bat-wing” Typical pattern of “renal” edema: “bat-wing”

distributiondistribution Translation: central, nongravitational Translation: central, nongravitational

distribution of edemadistribution of edema

Milne E, Pistolesi M, Miniati M, Guintini C. The radiologic distinction of cardiogenic and noncardiogenic pulmonary edema. AJR 1985, 144:879-94

Pulmonary Edema in CKD con’tPulmonary Edema in CKD con’t

Gluecker T, et al. Clinical and radiologic features of pulmonary edema. Radiographics 1999; 19: 1507-31

“Bat-wing” distribution

Pulmonary Edema in CKD con’tPulmonary Edema in CKD con’t

Caveats for “renal” edema in “bat-wing” Caveats for “renal” edema in “bat-wing” distribution: distribution: ““Bat-wing” pattern is not specific to renal failure:Bat-wing” pattern is not specific to renal failure:

• It can occur with rapidly developing severe cardiac failure as It can occur with rapidly developing severe cardiac failure as seen in acute mitral insufficiency (associated with papillary seen in acute mitral insufficiency (associated with papillary muscle rupture, massive myocardial infarct, and valve leaflet muscle rupture, massive myocardial infarct, and valve leaflet destruction due to septic endocarditis)destruction due to septic endocarditis)

Not all “renal” edemas present with “bat-wing” Not all “renal” edemas present with “bat-wing” distributiondistribution

• Experimental and clinical studies with CT, performed during Experimental and clinical studies with CT, performed during pulmonary edema of various origins, have demonstrated a pulmonary edema of various origins, have demonstrated a large variety of distribution for the pulmonary opacitieslarge variety of distribution for the pulmonary opacities

Gavelli, ibid

SummarySummary Chronic Kidney Disease is a relatively common disease Chronic Kidney Disease is a relatively common disease

in the US in the US One common thoracic manifestation of CKD is One common thoracic manifestation of CKD is

pulmonary metastatic calcificationpulmonary metastatic calcification Little is known about the pathogenesis or natural history Little is known about the pathogenesis or natural history

of metastatic calcification of metastatic calcification It is important to consider pulmonary calcification when It is important to consider pulmonary calcification when

working up a patient with CKD and an abnormal CXRworking up a patient with CKD and an abnormal CXR Metastatic calcification can be mistaken for other Metastatic calcification can be mistaken for other

common thoracic manifestations of CKD, including common thoracic manifestations of CKD, including bronchopulmonary infection or pulmonary edemabronchopulmonary infection or pulmonary edema

HRCT and HRCT and 99m99mTc-MDP Bone Scintigraphy can be used to Tc-MDP Bone Scintigraphy can be used to differentiate pulmonary calcification from other disease differentiate pulmonary calcification from other disease processes processes

CKD Pulmonary

Documents

Transcript of CKD Pulmonary