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Imaging the Chronic Kidney Disease Patient
C H A P T E R
75 Imaging the Chronic Kidney Disease Patient: Clinical Approaches, Utility and Complications David C. Wymer University of Florida, Malcom Randall VAMC, Gainesville, FL, USA
UTILITY OF IMAGING MODALITIES
INTRODUCTION Other than to document renal size and some complications of chronic disease such as kidney stones, imaging has historically had a limited role in CKD patients, with most evaluation based on laboaratory tests and renal biopsies. However, with newer modalities, imaging plays an increasingly vital role in assessing both renal function and structure in CKD. Diagnosis, disease status, disease progression, and development of complications of CKD are monitored clinically as well as with laboratory studies and radiologic imaging. While ultrasound and nuclear medicine have historically played a vital first role, newer magnetic resonance imaging (MRI) technologies promise to provide safe advanced functional renal analysis. With the sophisticated new MRI sequences we are on the verge of major changes in the evaluation and follow-up of patients with renal disease. Patients with CKD can be broadly separated into those with chronic but potentially controllable bilateral or unilateral disease processes, such as arteriosclerotic vascular disease, infections and stone disease, and those who have a systemic, progressive and bilateral process such as diabetes, hypertension and collagen vascular diseases. The indications for evaluating the kidneys include assessments of treatable cause of kidney disease (such as hydronephrosis), documentation of renal size, identification of the position of the kidneys (for biopsy), monitoring progression of disease, or identification or confirmation of a specific disease entity (such as polycystic kidney disease or renal vascular disease). P. Kimmel & M. Rosenberg (Eds): Chronic Renal Disease. DOI: http://dx.doi.org/10.1016/B978-0-12-411602-3.00075-5
Modality Selection There are many clinical scenarios which bring a CKD patient in for radiologic evaluation. The testing is specific for patient complaints. Guidelines for imaging are available online through the American College of Radiology. These are regularly updated (http://www. acr.org/Quality-Safety/Appropriateness-Criteria). The website is organized by signs and symptoms, and suggests the most useful modality as well as contraindications, relative contraindications and caveats for each modality.
Ultrasound Ultrasound is often the first imaging modality used in evaluating the kidneys, especially in patients with decreased renal function, because it is inexpensive, quick, safe, and easily accessible.1 In chronic renal infections and stone disease, the ultrasound shows findings referable to the disease process – such as abscesses, calculi and hydronephrosis. Early in the course of systemic renal failure the ultrasound exam is often normal. Depending on the underlying disease state, later imaging shows variable changes. Obstruction causing renal failure is readily identified by demonstration of hydronephrosis. Ultrasound allows measurements of kidney size and cortical thickness. Both are important measures in CKD. Plain films (KUB) and intravenous urography overestimate renal size, since
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2015 Elsevier Inc. All rights reserved. © 2012
Utility of ImaGing Modalities
891
X-ray procedures have an inherent magnification of approximately 25%. Due to operator dependence, it is generally felt computed tomography (CT) and MRI give more accurate overall renal measurements than ultrasound. Nevertheless, ultrasound is available, rapid and accurate enough for screening and following renal size. While there are size differences related to age, gender and body mass index, in the average adult the kidneys should measure about 11–12 cm in greatest length. Width measurements are variable and are not generally considered clinically useful. The cortex from renal margin to calyx should be about 1.5 cm in the mid-kidney and 3 cm at the poles. Lower measurements represent atrophy. The ultrasound appearance of normal kidneys typically shows well-marginated kidneys with a uniform cortex which is less echogenic than adjacent liver. The renal hilus is of increased echogenicity due to the presence of renal sinus fat and fibrous tissue (Figure 75.1). In most chronic diseases, ultrasound of the kidneys shows non-specific small and echogenic kidneys (Figure 75.2). However the ultrasound in chronic polycystic kidneys shows enlarged kidneys which are nearly
completely replaced with cysts (Figure 75.3). Most patients with CKD are middle aged and older. It is estimated that approximately 50% of adults have an incidental renal lesion. The most common incidental renal lesion is a cyst. Renal cysts are common and seen in otherwise normal patients. These are readily demonstrated and evaluated with ultrasound. Benign cysts are sharply circumscribed and may have thin internal septations (Figure 75.4). Contrast-enhanced ultrasound with microbubbles is being investigated.2 While it is being used in other parts of the world, it is an off-label use in the US at this time. Contrast-enhanced ultrasound with microbubbles is useful in evaluating renal blood flow (such as for the evaluation for renal artery stenosis) and more especially the degree of vascularity of complex real cysts and masses, allowing classification for malignant potential without the risk of contrast toxicity seen in CT and MRI.3
FIGURE 75.1 Normal renal ultrasound.
FIGURE
Nuclear Medicine Nuclear scintigraphy techniques evaluate renal function and to a lesser extent anatomy. Because of the
75.3 Numerous simple cysts replacing the renal
parenchyma.
FIGURE 75.2 Bilaterally small kidneys with thinned cortex.
FIGURE 75.4 Benign renal cortical cyst with single thin internal septation.
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75. Imaging the Chronic Kidney Disease Patient: Clinical Approaches, Utility and Complications
extremely small quantities injected and the benign nature of the radionuclides, these scans can be safely performed even in the face of markedly reduced renal function. Radioactive tracers are used which accumulate in the renal tissues based on the underlying physiologic functions of the differing renal structures. For example, GFR is evaluated with 99mTc-DTPA, tubular secretion with 99m Tc-MAG3, general cortical integrity with 99mTc-DMSA, and renal parenchymal inflammation with 67Ga-citrate. One of the strengths of nuclear imaging is that unlike the relative contraindications for contrast enhanced CT and MRI, it can be used even in the face of declining renal function. Due to the relative preservation of tubular function and increased extraction efficiency compared to 99mTc-DTPA, 99mTc-MAG3 continues to provide information in the face of declining renal function. 67 Gallium-citrate has been used to diagnose interstitial nephritis as well as chronic infection of the kidneys.4,5 The usual functional renal scan is performed with 99m Tc-MAG3, and can be studied in three phases of scanning. Following bolus intravenous injection of the nuclide, rapid sequential images are obtained to evaluate blood flow, which may be unilaterally or bilaterally compromised. Subsequent continued static imaging provides information on renal cortical function, both of the individual kidney as well as the differential function between the kidneys. On subsequent delayed imaging, the excretion through the collecting system to the urinary bladder is displayed to evaluate the presence of obstructive uropathy. The renogram curve reflects abnormalities of vascular flow, renal function and the presence of urinary tract obstruction. A normal curve of renal activity obtained during scanning is seen in Figure 75.5.
Computed Tomography CT has a limited role in patients in the later stages of CKD. Generally, if the eGFR is below 30 mL/min/1.73 m2, B
Normal renogram C
A
A - vascular phase B - cortical function phase C - excretory phase Time to peak should be 3–5 minutes peak to half empty = 10–12 minutes
Minutes 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
FIGURE 75.5 Normal renogram diagram showing different phases of renal nuclide clearance.
contrast material should not be given. Contrast can be judiciously used if the eGFR is 30 to 60 mL/min/1.73 m2. If contrast is administered, patients should be hydrated before, during and after contrast with intravenous saline and/or bicarbonate solution to reduce the risk of contrast-induced nephropathy. Another disadvantage of CT scanning which is increasingly recognized as important is the associated radiation dose. Protocols are being changed to reduce dose exposure and new data reconstruction software is now available which has significantly reduced the overall radiation exposures, but imaging with ultrasound and MRI which do not involve ionizing radiation are preferred whenever possible. In earlier stages of chronic infectious kidney disease, such as in patients with xanthogranulomatous pyelonephritis, non-contrast CT can aid in determining extent of disease and for preoperative planning. Non-contrast CT is also used in evaluating, diagnosing and following renal stone disease and nephrocalcinosis, and in guiding procedures such as renal biopsy and percutaneous nephrostomies. Newer CT equipment has dual energy scanning capability. This refers to simultaneous scanning using two distinct CT X-ray energies. Using the differential energy absorption of various renal stones, the mineral content of the stone can be non-invasively determined and appropriate therapy instituted, without having to physically remove and test the stone.
Magnetic Resonance Imaging While it is not the usual first test in evaluation of the chronically diseased kidney, MRI is undergoing rapid technological change which is making it attractive as a renal imaging agent even in patients with CKD.6,7 The ability to directly image in multiple planes allows excellent morphologic analysis. Imaging is based on the magnetic spin of hydrogen atoms, which are abundant in water-based tissues. Different sequences are used to highlight different structures such as cysts (water), fat or other soft tissues. Magnetic resonance angiography (MRA) visualizes flowing blood, and can even quantitate the velocity and flow rate in vessels.8,9,10 MRA can be performed with or without the intravenous administration of contrast material, although contrast usually provides better images. However, some of the new non-contrast sequences provide excellent vascular definition without the risk of contrast toxicity. By varying contrast injection timing and type of sequences, the abdominal venous structures can be visualized in addition to arteries. MRA is performed to evaluate the renal arteries for stenosis. MRA is less invasive than catheter angiography. With newer equipment and software, MRA now gives sensitivity of 97% and specificity of 93%, compared with
IX. SPECIAL CONSIDERATIONS
Utility of ImaGing Modalities
digital subtraction angiography for contrast-enhanced MRA in the detection of renal artery stenosis.8,9 MRA without gadolinium historically has had a lower sensitivity (53% to 100%) and specificity (65% to 97%) for detection of renal artery stenosis,9,10 but this difference is becoming less with development of new non-contrast sequences. This makes MRA without gadolinium one of the best available tests for evaluating the renal vasculature in patients with hypertension, poor renal function or allergies to intravenous contrast. With the appropriate timing of dialysis, CT angiography using contrast material can be performed in patients with severe decrements in renal function for surgical planning. However, MR imaging is often preferred before renal transplantation to evaluate the arteries (number and location), veins (number and location), and ureters (possible duplicated systems). Multiple other sophisticated sequences have been developed and are being studied. While functional analysis used to require intravenous gadolinium, which is contraindicated in severe renal failure, there are new sequences and contrast agents which do not have these drawbacks. One sequence called diffusion weighted imaging (DWI) displays the relative rate of diffusion of hydrogen atoms (mainly as water) through tissue. Various tissues have different diffusibility characteristics, which give different imaging appearances. Diffusion imaging has historically been most extensively studied in the brain, and has been shown to be sensitive to both cellular edema and cellular atrophy, and hence to the tissue damage typically induced by acute or chronic hypoxia. Many causes of CKD have relationships with relative hypoxia, such as that seen in diabetes. This relationship is being studied with the idea of using DWI MRI to evaluate and follow disease processes in the kidney.11 Several studies have already shown DWI abnormalities in the renal cortex and medulla in patients with CKD as well as in states of obstructive uropathy.12 Abnormalities are also seen in renal allografts, suggesting its use in transplant follow-up without the need for contrast.13 Research is ongoing to assess how this can be used clinically to differentiate various benign and malignant processes, as well as to potentially evaluate systemic disease states of the renal parenchyma. Another developing tool in MRI is blood oxygen level-dependent (BOLD) imaging.14 BOLD contrast imaging sequences can non-invasively demonstrate the level of intrarenal oxygen tension. Since oxygen delivery correlates with reserve capacity of the kidney and renal tubular workload capacity, BOLD imaging provides further analysis of underlying renal parenchymal function in normal and disease states. The clinical
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utility of BOLD imaging awaits further experimental validation. Magnetic resonance elastography (MRE) is a technique that images the propagation of shear waves through tissue.15 Tissue motion is mechanically induced and the resultant tissue displacement is proportional to the elastic properties of the imaged tissue. An MRI parametric image map can be displayed which correlates to organ “stiffness.” Ultrasound elastography is analogous and is also being investigated for evaluation of CKD patients. In CKD, one of the common final pathways is interstitial fibrosis, which can be semiquantitatively analyzed with MRE. Elastography with MR and ultrasound are not in common use for kidney studies and are still being studied experimentally. One final developing tool is used in evaluating intrarenal inflammation. In current clinical practice, the degree of inflammatory response in the kidney can be demonstrated only by renal biopsy. Infiltration of the glomeruli and interstitium by inflammatory cells is a common finding in both glomerulosclerosis and tubulointerstitial nephritis. Diffuse interstitial macrophage infiltration of the parenchyma is well documented in many chronic renal diseases and has shown good correlation with renal transplant graft rejection. There are developing methods of imaging the inflammatory response with MRI by taking advantage of the fact that macrophages take up particles, such as ultrasmall particles of iron oxide (USPIO).16 Being paramagnetic, these particles result in fairly pronounced decreased signal intensity on MRI in any tissues in which they accumulate. Delayed imaging following USPIO intravenous injection with MR imaging in cases of intrarenal inflammation demonstrates a diffuse but significant decrease of signal intensity throughout the kidney, slightly more pronounced in the cortex. To date the majority of studies have been in animal models, but some human trials are ongoing.
Imaging to Diagnose Disease States The normal aging kidney does not demonstrate significant pathologic changes other than some very minor decrease in size. Therefore any variation from the normal appearance seen on imaging reflects some disease state. The challenge is to diagnose disease or at least to exclude some differential considerations. There are a few classic renal appearances seen, such as the large echogenic kidney of HIV nephropathy17,18 (Figure 75.6), the large cystic kidneys of polycystic kidney disease (Figure 75.3) and the renal vascular stenosis of renal artery hypertension.9 The majority of renal disease states, however, have similar end results, such as parenchymal abnormalities which
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75. Imaging the Chronic Kidney Disease Patient: Clinical Approaches, Utility and Complications
FIGURE 75.6 Large, intensely echogenic kidney with HIV nephropathy.
give similar imaging findings of small kidneys, increased ultrasound echogenicity, intrarenal arterial flow restriction due to interstitial processes, and general decreased functional clearance of contrast or radionuclides. Renal angiography typically plays a limited role in CKD except in the evaluation and treatment of renal vascular disease – especially stenosis which may cause hypertension or even eventual renal failure from decreased blood flow. Other than the finding of renovascular stenosis, long-standing failure is angiographically seen as pruned and tortuous intrarenal vessels, diminished overall flow, and thinned cortex. Certain systemic diseases which lead to CKD have characteristic microaneurysms such as seen in Wegener’s granulomatosis, polyarteritis nodosa and systemic lupus erythematosus. Imaging can also be helpful for monitoring disease progression, and in some cases to corroborate a diagnosis or differentiate between possible diagnoses. This involves imaging organs other than the kidney, which may demonstrate diagnostic changes in certain diseases. For example, in the cardiorenal syndrome the chest X-ray, echocardiogram, chest CT or cardiac MRI can show changes of congestive failure, dilated nonischemic cardiomyopathy, or dilated ischemic cardiomyopathy as well as specific causes of heart failure such as cardiac sarcoidosis or amyloidosis. In the hepatorenal syndrome, the liver is usually expected to show a small, irregular, dense, fibrotic cirrhotic appearance, with flow abnormalities in the portal system and portal venous hypertension. Patients with sickle cell disease, in its advanced stages, can show splenic and bone infarctions as well as other classic bone changes such as the “fish mouth” vertebral appearance. Many of the collagen vascular diseases have other organ involvement, especially lung parenchymal infiltrates or pulmonary fibrosis.
FIGURE 75.7 Large upper pole renal stone with distal acoustical shadowing.
IMAGING CKD COMPLICATIONS The most commonly associated complication of CKD discerned radiologically is renal calcifications. Calcifications can occur in the collecting systems as nephrolithiasis and in the renal parenchyma as nephrocalcinosis. Most renal calculi are calcium oxalate, calcium phosphate, urate, struvite or cystine. The majority of stones contain calcium and are radio-opaque. Ultrasound is relatively insensitive to stone detection, but when seen, the stones are very echogenic and classically demonstrate “shadowing” distal to the stone due to blocking of the ultrasound wave (Figure 75.7). Stones can be reasonably differentiated using CT scanning by dualenergy CT. Ultrasound is non-invasive without associated radiation, and can be used in the initial evaluation of renal stones, especially in looking for hydronephrosis. Ultrasound, however, has a low sensitivity particularly for small stones and ureteral stones. Non-contrast CT is the imaging method of choice for evaluating the location and size of renal calculi, as well as obstructive uropathy. These parameters affect treatment options. In differentiation from nephrolithiasis, nephrocalcinosis refers to more diffuse intrarenal calcium. This process is commonly bilateral and can be seen in such states with medullary deposition in hyperparathyroidism, renal tubular acidosis, medullary sponge kidney and in some medication complications such as patients treated with acetazolamide. Cortical nephrocalcinosis is usually dystrophic in nature and is secondary to parenchymal tissue destruction such as seen with infarction and infection. Common etiologies include chronic glomerulonephritis, cortical necrosis, and transplant rejection. Osseous abnormalities are common in patients with CKD. These bone abnormalities can have various
IX. SPECIAL CONSIDERATIONS
Contrast Use in CKD
radiographic findings. Osteitis fibrosa is a manifestation of hyperparathyroidism from CKD, and results in the formation of cyst-like areas of brown tumors. Other typical findings in hyperparathyroidism include osteosclerosis of the vertebra (giving an X-ray appearance of the so-called rugger jersey spine), subperiosteal bone resorption (seen especially in the digits and clavicles) and skull changes (with scattered lytic and ground glass appearance). Extraskeletal calcifications from abnormalities of calcium-phosphate metabolism result in vascular, lung and periarticular calcium deposition. Osteomalacia results from abnormal mineralization. Osteomalacia can result in looser zones or pseudofractures, usually seen in the long bones of the extremities. Osteopenia and osteoporosis with abnormal bone density is common in patients with CKD. Imaging with dual energy X-ray absorptiometry (DEXA) is excellent at diagnosing demineralization, but it cannot differentiate the demineralization specific to CKD from other more common causes of osteoporosis. Bone biopsy is required for further differentiation and diagnosis. There are multiple neurologic abnormalities associated with CKD, but imaging is of little help in the specific evaluation and diagnosis of CKD-induced changes. MRI of the brain can show white matter changes in some cases with uremic encephalopathy. Such changes can reverse following regular dialysis. Cardiovascular abnormalities result from vascular inflammation as well as abnormal calcium metabolism, with accelerated progression of arteriosclerotic disease of vessels throughout the body as well as coronary vessels and cardiac valves. Screening for cardiac disease as well as risk stratification is possible with coronary calcium scoring with CT, cardiac CTA, stress echocardiography and nuclear myocardial perfusion imaging. These studies have been validated as independent predictors of cardiac morbidity and/or mortality.
CONTRAST USE IN CKD Caution must be exercised in the use of both the iodinated intravascular contrast used for CT and angiography, as well as gadolinium-based contrast used in MRI. While it is considered controversial, many experts suggest the risks of adverse events with iodinated contrast can be ameliorated with judicious use of dialysis as needed. However, the complications of nephrogenic systemic sclerosis (NSF) seen in patients following gadolinium contrast injection in patients with advanced renal insufficiency can be devastating. The first cases of NSF clinical findings were identified in 1997. An international NSF registry was developed at Yale University which maintains records on over 215 patients with NSF worldwide.
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NSF with pathological descriptions was reported in 2000.19 Evidence for a link between NSF and gadolinium was first described in a case series of 13 patients, all of whom developed NSF after being exposed to gadolinium.20 The background and history of NSF is nicely discussed in a recent review article.21 The reported incidence of NSF varies with individual gadolinium-based agents, primarily related to the degree of binding of the gadolinium chelate. Some of the newer agents are so tightly bound that it is suggested that they can be used safely in patients with advanced renal failure.22 The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) updated their consensus guidelines in 2012.23 In summary, those guidelines suggest that gadolinium-based agents can be separated by risk of NSF, based on the molecular structure of the individual contrast agents. Conservative strategies include contraindication in patients with stage 4 and 5 CKD (GFR <30 mL/ min/1.73m2), acute renal insufficiency as well as pregnant women and neonates, and use with caution in stage 3 CKD (GFR 30–60 mL/min/1.73m2) and children less than 1 year old. There should be at least 7 days between two injections. Lactating women should stop breastfeeding for 24 hours. The dose should not exceed 0.1 mmol/kg per examination. The committee states that newer gadolinium agents which are more tightly bound in the molecular structure such as gadobutrol, gadoterate, and gadoteridol may be used with caution in patients with stage 4 and 5 CKD since there are no well-documented unconfounded cases of NSF reported with these agents. The guidelines for use of iodinated contrast identify patients as being at risk for contrast induced nephropathy (CIN) as those with eGFR below 60 mL/min/1.73 m2, before intra-arterial injections, and eGFR less than 45 mL/min/1.73 m2 before intravenous injections. There is additional concern when the patient has underlying diabetic nephropathy, dehydration, congestive heart failure, is over the age of 70, or has had concurrent use of nephrotoxic drugs. In patients at risk, it is recommended that alternative imaging methods be explored. If contrast is to be used, low or iso-osmolar contrast at the lowest possible dose is recommended. Volume expansion has shown some protective effects. One general protocol suggests 1.0–1.5 mL/kg/h of intravenous saline for at least 6 hours before and after contrast administration. It is notable that to date prophylaxis with renal vasodilators, cytoprotective drugs or other pharmacologic interventions has not proven efficacious against CIN. Early small studies suggested that the use of bicarbonate solutions helped to reduce the incidence of CIN.
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75. Imaging the Chronic Kidney Disease Patient: Clinical Approaches, Utility and Complications
However, the largest trial to date showed no benefit of sodium bicarbonate over normal saline.24 Specific guidelines have also been defined for contrast use in patients with reduced renal function taking metformin. This is because of the possibility of metformininduced lactic acidosis. Since metformin is cleared by the kidneys, any reduction in renal function prolongs the biologic half-time of metformin and increases the subsequent risk of life-threatening acidosis. For these reasons drug guidelines contraindicate the use of metformin in patients with eGFR less than 30 mL/min/1.73 m2. The guidelines recommend that patients receiving IV contrast and with eGFR greater than 45 mL/min/1.73 m2 can continue taking metformin normally.23 However, patients receiving intra-arterial contrast and those with eGFR between 30 and 45 mL/ min/1.73 m2 should stop metformin 48 hours before the study and not begin metformin again until 48 hours after the study, and then only after determining that renal function has not deteriorated.
CONCLUSION Imaging plays an increasingly vital role in measuring both renal function and structure in patients with CKD. Diagnosis, disease status, disease progression, and development of complications of renal failure are monitored clinically as well as with laboratory studies and radiologic imaging. While ultrasound and nuclear medicine have historically played a vital first role, newer MRI technologies promise to provide safe advanced functional renal analysis. With sophisticated new MRI sequences we are on the verge of major changes in the radiologic evaluation and follow-up of patients with CKD. The indications for evaluating the kidneys include evaluation of treatable cause of failure (such as hydronephrosis), documentation of renal size, identification of the position of the kidneys, monitoring progression of disease, and identification or confirmation of a specific renal disease.
References 1. Buturovic´-Ponikvar J, Višnar-Perovicˇ A. Ultrasonography in chronic renal failure. Eur J Radiol 2003;46(2):115–22. Available from:. 2. Ascenti G, Mazziotti S, Zimbaro G, dSettineri N, Magno C, Melloni D, et al. Complex cystic renal masses: characterization with contrast-enhanced US. Radiology 2007;243(1):158–65. 3. Tamai H, Takiguchi Y, Oka M, Shingaki N, Enomoto S, Shiraki T, et al. Contrast-enhanced ultrasonography in the diagnosis of solid renal tumors. J Ultrasound Med 2005;24(12):1635–40. 4. Border WA, Holbrook JH, Peterson MC. Gallium citrate Ga 67 scanning in acute renal failure. West J Med 1995;162:477–8.
5. Joaquim AI, Mendes GEF, Ribeiro PFF, Baptista MAF, Burdmann EA. Ga-67 scintigraphy in the differential diagnosis between acute interstitial nephritis and acute tubular necrosis: an experimental study. Nephrol Dial Transplant 2010;25(10):3277–82. 6. Grenier N, Hauger O, Delmas Y, Combe C. MR imaging of nephropathies. Abdom Imaging 2006;31(2):213–23. 7. Cheong B, Muthupillai R, Rubin MF, Flamm SD. Normal values for renal length and volume as measured by magnetic resonance imaging. CJASN 2007;2(1):38–45. 8. Tan KT, van Beek EJ, Brown PW, van Delden OM, Tijssen J, Ramsay LE. Magnetic resonance angiography for the diagnosis of renal artery stenosis: A meta-analysis. Clin Radiol 2002;7(7):617–24. 9. Grenier N, Trillaud H. Comparison of imaging methods for renal artery stenosis. BJU Int 2000;86(suppl 1):84–94. 10. Marcos HB, Choyke PL. Magnetic resonance angiography of the kidney. Semin Nephrol 2000;20:450–5. 11. Namimoto T, Yamashita Y, Mitsuzaki K, Nakayama Y, Tang Y, Takahashi M. Measurement of the apparent diffusion coefficient in diffuse renal disease by diffusion-weighted echo-planar MR imaging. J Magn Reson Imaging 1999;9:832–7. 12. Bozgeyik Z, Kocakoc E, Sonmezgoz F, Diffusion-weighted MR. Imaging findings of kidneys in patients with early phase of obstruction. Eur J Radiol 2009;70:138–41. 13. Thoeny HC, Zumstein D, Simon-Zoula S, Eisenberger U, De Keyzer F, Hofmann L, et al. Functional evaluation of transplanted kidneys with diffusion-weighted and BOLD MR imaging: initial experience. Radiology 2006;241:812–21. 14. Prasad PV, Edelman RR, Epstein FH. Noninvasive evaluation of intrarenal oxygenation with BOLD MRI. Circulation 1996;94:3271–5. 15. Nihar SS, Scott AK, Donna JL, Gerard F, John CL, Bernard FK, et al. Evaluation of renal parenchymal disease in a rat model with magnetic resonance elastography. Magn Reson Med 2004;52:56–64. 16. Hauger O, Grenier N, Deminère C, Lasseur C, Delmas Y, Merville P, et al. USPIO-enhanced MR imaging of macrophage infiltration in native and transplanted kidneys: initial results in humans. Eur Radiol 2007;17(11):2898–907. 17. Herman ES, Klotman PE. HIV-associated nephropathy: epidemiology, pathogenesis, and treatment. RadioGraphics 2008;28:1339–54. 18. Herman ES1, Klotman PE, HIV nephropathy secondary to direct renal infection, complications (cancer) or secondary to antiviral Tx. Semin Nephrol 2003;23(2):200–8. 19. Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000;356:1000–1. 20. Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 2006;17(9):2359–62. 21. Thomsen HS. Nephrogenic systemic fibrosis: history and epidemiology. Radiol Clin North Am 2009;47(5):827–31. 22. Thomsen HS, Marckmann P, Logager VB. Update on nephrogenic systemic fibrosis. Magn Reson Imaging Clin N Am 2008;16:551–60. 23. Stacul F, van der Molen AJ, Reimer P, Webb JA, Thomsen HS, Morcos SK, et al. Contrast induced nephropathy: updated ESUR Contrast Media Safety Committees guidelines. Eur Radiol 2011;21:2527–41. 24. Brar SS, Shen AY, Jorgensen MB, Kotlewski A, Aharonian VJ, Desai N, et al. Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: a randomized trial. JAMA 2008;300(9):1038–46.
IX. SPECIAL CONSIDERATIONS
75 Imaging the Chronic Kidney Disease Patient: Clinical Approaches, Utility and Complications David C. Wymer University of Florida, Malcom Randall VAMC, Gainesville, FL, USA
UTILITY OF IMAGING MODALITIES
INTRODUCTION Other than to document renal size and some complications of chronic disease such as kidney stones, imaging has historically had a limited role in CKD patients, with most evaluation based on laboaratory tests and renal biopsies. However, with newer modalities, imaging plays an increasingly vital role in assessing both renal function and structure in CKD. Diagnosis, disease status, disease progression, and development of complications of CKD are monitored clinically as well as with laboratory studies and radiologic imaging. While ultrasound and nuclear medicine have historically played a vital first role, newer magnetic resonance imaging (MRI) technologies promise to provide safe advanced functional renal analysis. With the sophisticated new MRI sequences we are on the verge of major changes in the evaluation and follow-up of patients with renal disease. Patients with CKD can be broadly separated into those with chronic but potentially controllable bilateral or unilateral disease processes, such as arteriosclerotic vascular disease, infections and stone disease, and those who have a systemic, progressive and bilateral process such as diabetes, hypertension and collagen vascular diseases. The indications for evaluating the kidneys include assessments of treatable cause of kidney disease (such as hydronephrosis), documentation of renal size, identification of the position of the kidneys (for biopsy), monitoring progression of disease, or identification or confirmation of a specific disease entity (such as polycystic kidney disease or renal vascular disease). P. Kimmel & M. Rosenberg (Eds): Chronic Renal Disease. DOI: http://dx.doi.org/10.1016/B978-0-12-411602-3.00075-5
Modality Selection There are many clinical scenarios which bring a CKD patient in for radiologic evaluation. The testing is specific for patient complaints. Guidelines for imaging are available online through the American College of Radiology. These are regularly updated (http://www. acr.org/Quality-Safety/Appropriateness-Criteria). The website is organized by signs and symptoms, and suggests the most useful modality as well as contraindications, relative contraindications and caveats for each modality.
Ultrasound Ultrasound is often the first imaging modality used in evaluating the kidneys, especially in patients with decreased renal function, because it is inexpensive, quick, safe, and easily accessible.1 In chronic renal infections and stone disease, the ultrasound shows findings referable to the disease process – such as abscesses, calculi and hydronephrosis. Early in the course of systemic renal failure the ultrasound exam is often normal. Depending on the underlying disease state, later imaging shows variable changes. Obstruction causing renal failure is readily identified by demonstration of hydronephrosis. Ultrasound allows measurements of kidney size and cortical thickness. Both are important measures in CKD. Plain films (KUB) and intravenous urography overestimate renal size, since
890
2015 Elsevier Inc. All rights reserved. © 2012
Utility of ImaGing Modalities
891
X-ray procedures have an inherent magnification of approximately 25%. Due to operator dependence, it is generally felt computed tomography (CT) and MRI give more accurate overall renal measurements than ultrasound. Nevertheless, ultrasound is available, rapid and accurate enough for screening and following renal size. While there are size differences related to age, gender and body mass index, in the average adult the kidneys should measure about 11–12 cm in greatest length. Width measurements are variable and are not generally considered clinically useful. The cortex from renal margin to calyx should be about 1.5 cm in the mid-kidney and 3 cm at the poles. Lower measurements represent atrophy. The ultrasound appearance of normal kidneys typically shows well-marginated kidneys with a uniform cortex which is less echogenic than adjacent liver. The renal hilus is of increased echogenicity due to the presence of renal sinus fat and fibrous tissue (Figure 75.1). In most chronic diseases, ultrasound of the kidneys shows non-specific small and echogenic kidneys (Figure 75.2). However the ultrasound in chronic polycystic kidneys shows enlarged kidneys which are nearly
completely replaced with cysts (Figure 75.3). Most patients with CKD are middle aged and older. It is estimated that approximately 50% of adults have an incidental renal lesion. The most common incidental renal lesion is a cyst. Renal cysts are common and seen in otherwise normal patients. These are readily demonstrated and evaluated with ultrasound. Benign cysts are sharply circumscribed and may have thin internal septations (Figure 75.4). Contrast-enhanced ultrasound with microbubbles is being investigated.2 While it is being used in other parts of the world, it is an off-label use in the US at this time. Contrast-enhanced ultrasound with microbubbles is useful in evaluating renal blood flow (such as for the evaluation for renal artery stenosis) and more especially the degree of vascularity of complex real cysts and masses, allowing classification for malignant potential without the risk of contrast toxicity seen in CT and MRI.3
FIGURE 75.1 Normal renal ultrasound.
FIGURE
Nuclear Medicine Nuclear scintigraphy techniques evaluate renal function and to a lesser extent anatomy. Because of the
75.3 Numerous simple cysts replacing the renal
parenchyma.
FIGURE 75.2 Bilaterally small kidneys with thinned cortex.
FIGURE 75.4 Benign renal cortical cyst with single thin internal septation.
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75. Imaging the Chronic Kidney Disease Patient: Clinical Approaches, Utility and Complications
extremely small quantities injected and the benign nature of the radionuclides, these scans can be safely performed even in the face of markedly reduced renal function. Radioactive tracers are used which accumulate in the renal tissues based on the underlying physiologic functions of the differing renal structures. For example, GFR is evaluated with 99mTc-DTPA, tubular secretion with 99m Tc-MAG3, general cortical integrity with 99mTc-DMSA, and renal parenchymal inflammation with 67Ga-citrate. One of the strengths of nuclear imaging is that unlike the relative contraindications for contrast enhanced CT and MRI, it can be used even in the face of declining renal function. Due to the relative preservation of tubular function and increased extraction efficiency compared to 99mTc-DTPA, 99mTc-MAG3 continues to provide information in the face of declining renal function. 67 Gallium-citrate has been used to diagnose interstitial nephritis as well as chronic infection of the kidneys.4,5 The usual functional renal scan is performed with 99m Tc-MAG3, and can be studied in three phases of scanning. Following bolus intravenous injection of the nuclide, rapid sequential images are obtained to evaluate blood flow, which may be unilaterally or bilaterally compromised. Subsequent continued static imaging provides information on renal cortical function, both of the individual kidney as well as the differential function between the kidneys. On subsequent delayed imaging, the excretion through the collecting system to the urinary bladder is displayed to evaluate the presence of obstructive uropathy. The renogram curve reflects abnormalities of vascular flow, renal function and the presence of urinary tract obstruction. A normal curve of renal activity obtained during scanning is seen in Figure 75.5.
Computed Tomography CT has a limited role in patients in the later stages of CKD. Generally, if the eGFR is below 30 mL/min/1.73 m2, B
Normal renogram C
A
A - vascular phase B - cortical function phase C - excretory phase Time to peak should be 3–5 minutes peak to half empty = 10–12 minutes
Minutes 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
FIGURE 75.5 Normal renogram diagram showing different phases of renal nuclide clearance.
contrast material should not be given. Contrast can be judiciously used if the eGFR is 30 to 60 mL/min/1.73 m2. If contrast is administered, patients should be hydrated before, during and after contrast with intravenous saline and/or bicarbonate solution to reduce the risk of contrast-induced nephropathy. Another disadvantage of CT scanning which is increasingly recognized as important is the associated radiation dose. Protocols are being changed to reduce dose exposure and new data reconstruction software is now available which has significantly reduced the overall radiation exposures, but imaging with ultrasound and MRI which do not involve ionizing radiation are preferred whenever possible. In earlier stages of chronic infectious kidney disease, such as in patients with xanthogranulomatous pyelonephritis, non-contrast CT can aid in determining extent of disease and for preoperative planning. Non-contrast CT is also used in evaluating, diagnosing and following renal stone disease and nephrocalcinosis, and in guiding procedures such as renal biopsy and percutaneous nephrostomies. Newer CT equipment has dual energy scanning capability. This refers to simultaneous scanning using two distinct CT X-ray energies. Using the differential energy absorption of various renal stones, the mineral content of the stone can be non-invasively determined and appropriate therapy instituted, without having to physically remove and test the stone.
Magnetic Resonance Imaging While it is not the usual first test in evaluation of the chronically diseased kidney, MRI is undergoing rapid technological change which is making it attractive as a renal imaging agent even in patients with CKD.6,7 The ability to directly image in multiple planes allows excellent morphologic analysis. Imaging is based on the magnetic spin of hydrogen atoms, which are abundant in water-based tissues. Different sequences are used to highlight different structures such as cysts (water), fat or other soft tissues. Magnetic resonance angiography (MRA) visualizes flowing blood, and can even quantitate the velocity and flow rate in vessels.8,9,10 MRA can be performed with or without the intravenous administration of contrast material, although contrast usually provides better images. However, some of the new non-contrast sequences provide excellent vascular definition without the risk of contrast toxicity. By varying contrast injection timing and type of sequences, the abdominal venous structures can be visualized in addition to arteries. MRA is performed to evaluate the renal arteries for stenosis. MRA is less invasive than catheter angiography. With newer equipment and software, MRA now gives sensitivity of 97% and specificity of 93%, compared with
IX. SPECIAL CONSIDERATIONS
Utility of ImaGing Modalities
digital subtraction angiography for contrast-enhanced MRA in the detection of renal artery stenosis.8,9 MRA without gadolinium historically has had a lower sensitivity (53% to 100%) and specificity (65% to 97%) for detection of renal artery stenosis,9,10 but this difference is becoming less with development of new non-contrast sequences. This makes MRA without gadolinium one of the best available tests for evaluating the renal vasculature in patients with hypertension, poor renal function or allergies to intravenous contrast. With the appropriate timing of dialysis, CT angiography using contrast material can be performed in patients with severe decrements in renal function for surgical planning. However, MR imaging is often preferred before renal transplantation to evaluate the arteries (number and location), veins (number and location), and ureters (possible duplicated systems). Multiple other sophisticated sequences have been developed and are being studied. While functional analysis used to require intravenous gadolinium, which is contraindicated in severe renal failure, there are new sequences and contrast agents which do not have these drawbacks. One sequence called diffusion weighted imaging (DWI) displays the relative rate of diffusion of hydrogen atoms (mainly as water) through tissue. Various tissues have different diffusibility characteristics, which give different imaging appearances. Diffusion imaging has historically been most extensively studied in the brain, and has been shown to be sensitive to both cellular edema and cellular atrophy, and hence to the tissue damage typically induced by acute or chronic hypoxia. Many causes of CKD have relationships with relative hypoxia, such as that seen in diabetes. This relationship is being studied with the idea of using DWI MRI to evaluate and follow disease processes in the kidney.11 Several studies have already shown DWI abnormalities in the renal cortex and medulla in patients with CKD as well as in states of obstructive uropathy.12 Abnormalities are also seen in renal allografts, suggesting its use in transplant follow-up without the need for contrast.13 Research is ongoing to assess how this can be used clinically to differentiate various benign and malignant processes, as well as to potentially evaluate systemic disease states of the renal parenchyma. Another developing tool in MRI is blood oxygen level-dependent (BOLD) imaging.14 BOLD contrast imaging sequences can non-invasively demonstrate the level of intrarenal oxygen tension. Since oxygen delivery correlates with reserve capacity of the kidney and renal tubular workload capacity, BOLD imaging provides further analysis of underlying renal parenchymal function in normal and disease states. The clinical
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utility of BOLD imaging awaits further experimental validation. Magnetic resonance elastography (MRE) is a technique that images the propagation of shear waves through tissue.15 Tissue motion is mechanically induced and the resultant tissue displacement is proportional to the elastic properties of the imaged tissue. An MRI parametric image map can be displayed which correlates to organ “stiffness.” Ultrasound elastography is analogous and is also being investigated for evaluation of CKD patients. In CKD, one of the common final pathways is interstitial fibrosis, which can be semiquantitatively analyzed with MRE. Elastography with MR and ultrasound are not in common use for kidney studies and are still being studied experimentally. One final developing tool is used in evaluating intrarenal inflammation. In current clinical practice, the degree of inflammatory response in the kidney can be demonstrated only by renal biopsy. Infiltration of the glomeruli and interstitium by inflammatory cells is a common finding in both glomerulosclerosis and tubulointerstitial nephritis. Diffuse interstitial macrophage infiltration of the parenchyma is well documented in many chronic renal diseases and has shown good correlation with renal transplant graft rejection. There are developing methods of imaging the inflammatory response with MRI by taking advantage of the fact that macrophages take up particles, such as ultrasmall particles of iron oxide (USPIO).16 Being paramagnetic, these particles result in fairly pronounced decreased signal intensity on MRI in any tissues in which they accumulate. Delayed imaging following USPIO intravenous injection with MR imaging in cases of intrarenal inflammation demonstrates a diffuse but significant decrease of signal intensity throughout the kidney, slightly more pronounced in the cortex. To date the majority of studies have been in animal models, but some human trials are ongoing.
Imaging to Diagnose Disease States The normal aging kidney does not demonstrate significant pathologic changes other than some very minor decrease in size. Therefore any variation from the normal appearance seen on imaging reflects some disease state. The challenge is to diagnose disease or at least to exclude some differential considerations. There are a few classic renal appearances seen, such as the large echogenic kidney of HIV nephropathy17,18 (Figure 75.6), the large cystic kidneys of polycystic kidney disease (Figure 75.3) and the renal vascular stenosis of renal artery hypertension.9 The majority of renal disease states, however, have similar end results, such as parenchymal abnormalities which
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75. Imaging the Chronic Kidney Disease Patient: Clinical Approaches, Utility and Complications
FIGURE 75.6 Large, intensely echogenic kidney with HIV nephropathy.
give similar imaging findings of small kidneys, increased ultrasound echogenicity, intrarenal arterial flow restriction due to interstitial processes, and general decreased functional clearance of contrast or radionuclides. Renal angiography typically plays a limited role in CKD except in the evaluation and treatment of renal vascular disease – especially stenosis which may cause hypertension or even eventual renal failure from decreased blood flow. Other than the finding of renovascular stenosis, long-standing failure is angiographically seen as pruned and tortuous intrarenal vessels, diminished overall flow, and thinned cortex. Certain systemic diseases which lead to CKD have characteristic microaneurysms such as seen in Wegener’s granulomatosis, polyarteritis nodosa and systemic lupus erythematosus. Imaging can also be helpful for monitoring disease progression, and in some cases to corroborate a diagnosis or differentiate between possible diagnoses. This involves imaging organs other than the kidney, which may demonstrate diagnostic changes in certain diseases. For example, in the cardiorenal syndrome the chest X-ray, echocardiogram, chest CT or cardiac MRI can show changes of congestive failure, dilated nonischemic cardiomyopathy, or dilated ischemic cardiomyopathy as well as specific causes of heart failure such as cardiac sarcoidosis or amyloidosis. In the hepatorenal syndrome, the liver is usually expected to show a small, irregular, dense, fibrotic cirrhotic appearance, with flow abnormalities in the portal system and portal venous hypertension. Patients with sickle cell disease, in its advanced stages, can show splenic and bone infarctions as well as other classic bone changes such as the “fish mouth” vertebral appearance. Many of the collagen vascular diseases have other organ involvement, especially lung parenchymal infiltrates or pulmonary fibrosis.
FIGURE 75.7 Large upper pole renal stone with distal acoustical shadowing.
IMAGING CKD COMPLICATIONS The most commonly associated complication of CKD discerned radiologically is renal calcifications. Calcifications can occur in the collecting systems as nephrolithiasis and in the renal parenchyma as nephrocalcinosis. Most renal calculi are calcium oxalate, calcium phosphate, urate, struvite or cystine. The majority of stones contain calcium and are radio-opaque. Ultrasound is relatively insensitive to stone detection, but when seen, the stones are very echogenic and classically demonstrate “shadowing” distal to the stone due to blocking of the ultrasound wave (Figure 75.7). Stones can be reasonably differentiated using CT scanning by dualenergy CT. Ultrasound is non-invasive without associated radiation, and can be used in the initial evaluation of renal stones, especially in looking for hydronephrosis. Ultrasound, however, has a low sensitivity particularly for small stones and ureteral stones. Non-contrast CT is the imaging method of choice for evaluating the location and size of renal calculi, as well as obstructive uropathy. These parameters affect treatment options. In differentiation from nephrolithiasis, nephrocalcinosis refers to more diffuse intrarenal calcium. This process is commonly bilateral and can be seen in such states with medullary deposition in hyperparathyroidism, renal tubular acidosis, medullary sponge kidney and in some medication complications such as patients treated with acetazolamide. Cortical nephrocalcinosis is usually dystrophic in nature and is secondary to parenchymal tissue destruction such as seen with infarction and infection. Common etiologies include chronic glomerulonephritis, cortical necrosis, and transplant rejection. Osseous abnormalities are common in patients with CKD. These bone abnormalities can have various
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Contrast Use in CKD
radiographic findings. Osteitis fibrosa is a manifestation of hyperparathyroidism from CKD, and results in the formation of cyst-like areas of brown tumors. Other typical findings in hyperparathyroidism include osteosclerosis of the vertebra (giving an X-ray appearance of the so-called rugger jersey spine), subperiosteal bone resorption (seen especially in the digits and clavicles) and skull changes (with scattered lytic and ground glass appearance). Extraskeletal calcifications from abnormalities of calcium-phosphate metabolism result in vascular, lung and periarticular calcium deposition. Osteomalacia results from abnormal mineralization. Osteomalacia can result in looser zones or pseudofractures, usually seen in the long bones of the extremities. Osteopenia and osteoporosis with abnormal bone density is common in patients with CKD. Imaging with dual energy X-ray absorptiometry (DEXA) is excellent at diagnosing demineralization, but it cannot differentiate the demineralization specific to CKD from other more common causes of osteoporosis. Bone biopsy is required for further differentiation and diagnosis. There are multiple neurologic abnormalities associated with CKD, but imaging is of little help in the specific evaluation and diagnosis of CKD-induced changes. MRI of the brain can show white matter changes in some cases with uremic encephalopathy. Such changes can reverse following regular dialysis. Cardiovascular abnormalities result from vascular inflammation as well as abnormal calcium metabolism, with accelerated progression of arteriosclerotic disease of vessels throughout the body as well as coronary vessels and cardiac valves. Screening for cardiac disease as well as risk stratification is possible with coronary calcium scoring with CT, cardiac CTA, stress echocardiography and nuclear myocardial perfusion imaging. These studies have been validated as independent predictors of cardiac morbidity and/or mortality.
CONTRAST USE IN CKD Caution must be exercised in the use of both the iodinated intravascular contrast used for CT and angiography, as well as gadolinium-based contrast used in MRI. While it is considered controversial, many experts suggest the risks of adverse events with iodinated contrast can be ameliorated with judicious use of dialysis as needed. However, the complications of nephrogenic systemic sclerosis (NSF) seen in patients following gadolinium contrast injection in patients with advanced renal insufficiency can be devastating. The first cases of NSF clinical findings were identified in 1997. An international NSF registry was developed at Yale University which maintains records on over 215 patients with NSF worldwide.
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NSF with pathological descriptions was reported in 2000.19 Evidence for a link between NSF and gadolinium was first described in a case series of 13 patients, all of whom developed NSF after being exposed to gadolinium.20 The background and history of NSF is nicely discussed in a recent review article.21 The reported incidence of NSF varies with individual gadolinium-based agents, primarily related to the degree of binding of the gadolinium chelate. Some of the newer agents are so tightly bound that it is suggested that they can be used safely in patients with advanced renal failure.22 The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) updated their consensus guidelines in 2012.23 In summary, those guidelines suggest that gadolinium-based agents can be separated by risk of NSF, based on the molecular structure of the individual contrast agents. Conservative strategies include contraindication in patients with stage 4 and 5 CKD (GFR <30 mL/ min/1.73m2), acute renal insufficiency as well as pregnant women and neonates, and use with caution in stage 3 CKD (GFR 30–60 mL/min/1.73m2) and children less than 1 year old. There should be at least 7 days between two injections. Lactating women should stop breastfeeding for 24 hours. The dose should not exceed 0.1 mmol/kg per examination. The committee states that newer gadolinium agents which are more tightly bound in the molecular structure such as gadobutrol, gadoterate, and gadoteridol may be used with caution in patients with stage 4 and 5 CKD since there are no well-documented unconfounded cases of NSF reported with these agents. The guidelines for use of iodinated contrast identify patients as being at risk for contrast induced nephropathy (CIN) as those with eGFR below 60 mL/min/1.73 m2, before intra-arterial injections, and eGFR less than 45 mL/min/1.73 m2 before intravenous injections. There is additional concern when the patient has underlying diabetic nephropathy, dehydration, congestive heart failure, is over the age of 70, or has had concurrent use of nephrotoxic drugs. In patients at risk, it is recommended that alternative imaging methods be explored. If contrast is to be used, low or iso-osmolar contrast at the lowest possible dose is recommended. Volume expansion has shown some protective effects. One general protocol suggests 1.0–1.5 mL/kg/h of intravenous saline for at least 6 hours before and after contrast administration. It is notable that to date prophylaxis with renal vasodilators, cytoprotective drugs or other pharmacologic interventions has not proven efficacious against CIN. Early small studies suggested that the use of bicarbonate solutions helped to reduce the incidence of CIN.
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However, the largest trial to date showed no benefit of sodium bicarbonate over normal saline.24 Specific guidelines have also been defined for contrast use in patients with reduced renal function taking metformin. This is because of the possibility of metformininduced lactic acidosis. Since metformin is cleared by the kidneys, any reduction in renal function prolongs the biologic half-time of metformin and increases the subsequent risk of life-threatening acidosis. For these reasons drug guidelines contraindicate the use of metformin in patients with eGFR less than 30 mL/min/1.73 m2. The guidelines recommend that patients receiving IV contrast and with eGFR greater than 45 mL/min/1.73 m2 can continue taking metformin normally.23 However, patients receiving intra-arterial contrast and those with eGFR between 30 and 45 mL/ min/1.73 m2 should stop metformin 48 hours before the study and not begin metformin again until 48 hours after the study, and then only after determining that renal function has not deteriorated.
CONCLUSION Imaging plays an increasingly vital role in measuring both renal function and structure in patients with CKD. Diagnosis, disease status, disease progression, and development of complications of renal failure are monitored clinically as well as with laboratory studies and radiologic imaging. While ultrasound and nuclear medicine have historically played a vital first role, newer MRI technologies promise to provide safe advanced functional renal analysis. With sophisticated new MRI sequences we are on the verge of major changes in the radiologic evaluation and follow-up of patients with CKD. The indications for evaluating the kidneys include evaluation of treatable cause of failure (such as hydronephrosis), documentation of renal size, identification of the position of the kidneys, monitoring progression of disease, and identification or confirmation of a specific renal disease.
References 1. Buturovic´-Ponikvar J, Višnar-Perovicˇ A. Ultrasonography in chronic renal failure. Eur J Radiol 2003;46(2):115–22. Available from:
5. Joaquim AI, Mendes GEF, Ribeiro PFF, Baptista MAF, Burdmann EA. Ga-67 scintigraphy in the differential diagnosis between acute interstitial nephritis and acute tubular necrosis: an experimental study. Nephrol Dial Transplant 2010;25(10):3277–82. 6. Grenier N, Hauger O, Delmas Y, Combe C. MR imaging of nephropathies. Abdom Imaging 2006;31(2):213–23. 7. Cheong B, Muthupillai R, Rubin MF, Flamm SD. Normal values for renal length and volume as measured by magnetic resonance imaging. CJASN 2007;2(1):38–45. 8. Tan KT, van Beek EJ, Brown PW, van Delden OM, Tijssen J, Ramsay LE. Magnetic resonance angiography for the diagnosis of renal artery stenosis: A meta-analysis. Clin Radiol 2002;7(7):617–24. 9. Grenier N, Trillaud H. Comparison of imaging methods for renal artery stenosis. BJU Int 2000;86(suppl 1):84–94. 10. Marcos HB, Choyke PL. Magnetic resonance angiography of the kidney. Semin Nephrol 2000;20:450–5. 11. Namimoto T, Yamashita Y, Mitsuzaki K, Nakayama Y, Tang Y, Takahashi M. Measurement of the apparent diffusion coefficient in diffuse renal disease by diffusion-weighted echo-planar MR imaging. J Magn Reson Imaging 1999;9:832–7. 12. Bozgeyik Z, Kocakoc E, Sonmezgoz F, Diffusion-weighted MR. Imaging findings of kidneys in patients with early phase of obstruction. Eur J Radiol 2009;70:138–41. 13. Thoeny HC, Zumstein D, Simon-Zoula S, Eisenberger U, De Keyzer F, Hofmann L, et al. Functional evaluation of transplanted kidneys with diffusion-weighted and BOLD MR imaging: initial experience. Radiology 2006;241:812–21. 14. Prasad PV, Edelman RR, Epstein FH. Noninvasive evaluation of intrarenal oxygenation with BOLD MRI. Circulation 1996;94:3271–5. 15. Nihar SS, Scott AK, Donna JL, Gerard F, John CL, Bernard FK, et al. Evaluation of renal parenchymal disease in a rat model with magnetic resonance elastography. Magn Reson Med 2004;52:56–64. 16. Hauger O, Grenier N, Deminère C, Lasseur C, Delmas Y, Merville P, et al. USPIO-enhanced MR imaging of macrophage infiltration in native and transplanted kidneys: initial results in humans. Eur Radiol 2007;17(11):2898–907. 17. Herman ES, Klotman PE. HIV-associated nephropathy: epidemiology, pathogenesis, and treatment. RadioGraphics 2008;28:1339–54. 18. Herman ES1, Klotman PE, HIV nephropathy secondary to direct renal infection, complications (cancer) or secondary to antiviral Tx. Semin Nephrol 2003;23(2):200–8. 19. Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000;356:1000–1. 20. Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 2006;17(9):2359–62. 21. Thomsen HS. Nephrogenic systemic fibrosis: history and epidemiology. Radiol Clin North Am 2009;47(5):827–31. 22. Thomsen HS, Marckmann P, Logager VB. Update on nephrogenic systemic fibrosis. Magn Reson Imaging Clin N Am 2008;16:551–60. 23. Stacul F, van der Molen AJ, Reimer P, Webb JA, Thomsen HS, Morcos SK, et al. Contrast induced nephropathy: updated ESUR Contrast Media Safety Committees guidelines. Eur Radiol 2011;21:2527–41. 24. Brar SS, Shen AY, Jorgensen MB, Kotlewski A, Aharonian VJ, Desai N, et al. Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: a randomized trial. JAMA 2008;300(9):1038–46.
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