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Clinical and Radiographic Findings in a Patient With Chronic Kidney Disease

Erica Boettcher Radiology Elective November 2005

Case Presentation: Mr. B



47 yr-old man with Chronic Kidney Disease yrpresents with 3-months of nonproductive 3cough Also complains of mild breathlessness on exertion; otherwise feels well Denies fevers/chills/weight loss/hemoptysis No s/o sinus disease, asthma, GERD PPD non-reactive non-

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

Case: Mr. B cont


Chronic Kidney Disease

2/2 HTN Hemodialysis dependent x 4 years


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


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

Case: Mr. B cont


O2 sat 94% No JVD No lymphadenopathy Lungs clear CV exam normal No peripheral edema


serum Ca 9.5, phos 5.2, Hct 44%

Case: Mr. B cont

CXR reveals patchy areas of consolidative opacities bilaterally

Janssen WJ, ibid

Case: Mr. B cont

CT findings demonstrate R>L consolidative opacities

Janssen WJ, ibid

Case: Mr. B cont

What is the most likely diagnosis?

Case: Mr. B cont

Answer: Metastatic calcification secondary to chronic kidney disease

Case: Mr. B cont

Question #1: How does Chronic Kidney Disease cause calcification in the lungs? Question #2: Why is this important?

IntroductionIntroduction- Chronic Kidney Disease (CKD)  Metastatic pulmonary calcification  Other common thoracic manifestations of CKD that can mimic metastatic calcification  Bronchopulmonary infections  Pulmonary Edema  Summary

Chronic Kidney Disease

Magnitude of the disease:


Over the past several years there has been continued growth of the total number of CKD patients requiring dialysis Since 1988 the prevalent dialysis population has tripled 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

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

325,000 patients on dialysis 128,000 transplant patients

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

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? CalcificationCalcification=deposition of calcium salts in soft tissues  Organs most commonly affected: stomach, kidneys, lungs, heart, and blood vessels  Lungs are particularly susceptible  Metastatic calcification:

calcium deposits in normal tissues calcium deposits in previously damaged tissue seen in: granulomatous disorders such as tuberculosis, histoplasmosis,
coccidiomycosis, and sarcoidosis following infection such as pneumocystis and varicella with occupational lung diseases including silicosis and coal workers pneumoconiosis

Dystrophic calcification:

Metastatic Calcification-causes? Calcification 

Metastatic calcification is further divided into benign and malignant causes Benign Causes:

By far the most common: patients on hemodialysis for chronic kidney disease 6060-75% of chronic dialysis patients have some degree of pulmonary calcification at autopsy Other benign causes (rare): orthotopic liver transplantation, primary hyperparathyroidism, milkmilkalkali syndrome, hypervitaminosis D, osteopetrosis, Pagets disease

Janssen WJ, ibid

Proposed Mechanisms of Metastatic Lung Calcification


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

Elevated serum phosphorus and calcium levels (common in CKD, but levels correlate poorly with development of pulmonary calcification) Alkaline pH which favors precipitation of calcium phosphate in tissues (intermittent alkalosis follows bicarb hemodialysis) (intermittent Parathyroid hormone (removal of parathyroid glands from (removal laboratory animals with CKD prevents pulmonary calcinosis)

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. 1654-

Histology of Metastatic Lung Calcification


Linear calcific deposits in alveolar septal walls with secondary fibroproliferative response Calcification of the elastic lamina in small and medium-sized mediumpulmonary vessels and within bronchial basement membrane

Chan, ibid

Metastatic Calcification: CXR

While chest radiographs are useful for detection of pleural calcification, hilar-mediastinal lymph node hilarcalcification, and calcified lung nodules, they are less sensitive for parenchymal calcification For parenchymal calcification, CXR can reveal any of the following patterns:
Diffuse ground glass/reticular opacities, stable in time or slowly progressive (heart size and pulmonary vasculature normal) LowLow-density apical opacities Calcified nodules


Gavelli, ibid

Metastatic Calcification: CXR


CXR are unable to detect small amounts of calcium When compared with autopsy results, CXR demonstrate parenchymal calcification in <15% of patients 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 Abnormalities can also be mistaken for hemorrhage, infarct, or malignancy

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

Metastatic Calcification: Helpful Imaging

Preferred imaging:

HighHigh-resolution computer tomography (HRCT) scan 99mtechnetium-methylene diphosphate bone technetiumscintigraphy These modalities are more sensitive and specific than CXR for detection of pulmonary calcification

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

Metastatic Calcification: CT


Standard 7- or 10-mm-thick images may fail to 7- 10-mmdetect microscopic calcification due to signal averaging from normal adjacent tissue, therefore HRCT is preferred HRCT is relatively specific for pulmonary calcification Caveat: presence of dense lesions on lung window images will not distinguish between 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 hypercalcaemia: radiographs and CT scans. AJR 1994;162:799802. 1994;162:799

Metastatic Calcification: CT cont

 (1) (2) (3) 

Patterns seen on HRCT scan: diffuse or patchy ground-glass opacification grounddense consolidation, often in a lobar distribution, and multiple nodules in a diffuse or localized distribution These patterns are not mutually exclusive, and a combination of the different patterns may exist

Chan, ibid

Imaging: 99mTc-MDP Bone TcScintigraphy


to HRCT: Bone Scintigraphy  Highly specific for pulmonary calcification  Useful to sort out equivocal cases on HRCT (calcified vs noncalcified opacities) Bone scintigraphy of a patient with

Chan, ibid

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

Clinical Significance of Metastatic Calcification


By some reports, ~90% of patients with CKD have abnormal pulmonary function test results Most common abnormality is:

impaired diffusion capacity (decrease in DLCO)

Pulmonary calcification may contribute to these abnormalities by increasing vascular permeability and inducing interstitial fibrosis In some studies, tissue calcium content from biopsy specimens correlates strongly with reductions 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 Calcification cont


There are little data regarding the natural history of metastatic pulmonary calcification Majority of patients are asymptomatic but can present with dyspnea and cough Most often process is slowly progressive but pulmonary fibrosis, cor pulmonale, and respiratory failure develops in a minority of patients

Janssen, ibid

Clinical Significance of Metastatic Calcification cont


options are limited:

Therapy is aimed at correcting hypercalcemia and hyperphosphatemia


transplantation may lead to disease remission in some patients, while in others, the disease may progress despite normal functioning allograft

Hartman, ibid

Clinical Significance of Metastatic Calcification cont


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

Other Common Thoracic Complications of CKD


infections and

Pulmonary Edema  These can be indistinguishable from metastatic calcification on CXR

Bronchopulmonary infections

Infection is frequent cause of morbidity and mortality among patients with CKD and ESRD receiving dialysis In 2001 Sarnak and colleagues obtained data from 50,227 deaths from ESRD (years 199419941996) and 2.27 million deaths from general population (year 1993) Found that pulmonary infectious mortality is ~10~10fold higher in dialysis patients compared to general 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 cont


presentation of infection on CXR:

Nodular lesions and/or consolidation, either patchy or diffuse



Staphylococcal pneumonia Septic embolism Tuberculosis/Fungal Streptococcal 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 cont


reasons why dialysis patients may be particularly susceptible to pulmonary infections:


Pulmonary functional abnormalities Depressed cellular and humoral immunity Impaired phagocytic cell function

Sarnak, ibid

Pulmonary Edema in CKD

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

Pulmonary Edema in CKD cont


to Milne colleagues it is possible to distinguish, on CXR, cardiogenic from renal edema

Typical pattern of renal edema: bat-wing batdistribution Translation: central, nongravitational distribution 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 cont

Bat-wing distribution

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

Pulmonary Edema in CKD cont

Caveats for renal edema in bat-wing batdistribution:

BatBat-wing pattern is not specific to renal failure:

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)

Not all renal edemas present with bat-wing batdistribution

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

Gavelli, ibid


Chronic Kidney Disease is a relatively common disease in the US One common thoracic manifestation of CKD is pulmonary metastatic calcification Little is known about the pathogenesis or natural history of metastatic calcification It is important to consider pulmonary calcification when working up a patient with CKD and an abnormal CXR Metastatic calcification can be mistaken for other common thoracic manifestations of CKD, including bronchopulmonary infection or pulmonary edema HRCT and 99mTc-MDP Bone Scintigraphy can be used to Tcdifferentiate pulmonary calcification from other disease processes