Renal Relevant : Use of Ultrasonography in Patients with AKI

Sarah Faubel,* Nayana U. Patel,† Mark E. Lockhart,‡ and Melissa A. Cadnapaphornchai§

Summary As judged by the American College of Radiology Appropriateness Criteria, renal is the most appropriate imaging test in the evaluation of AKI and has the highest level of recommendation. Unfortunately, nephrologists are rarely specifically trained in ultrasonography technique and interpretation, and *Division of Internal Medicine, , important clinical information obtained from renal ultrasonography may not be appreciated. In this review, the University of Colorado strengths and limitations of grayscale ultrasonography in the evaluation of patients with AKI will be discussed and Denver Veterans with attention to its use for (1) assessment of intrinsic causes of AKI, (2) distinguishing acute from chronic Affairs Medical Center, 3 Denver, Colorado; diseases, and ( ) detection of obstruction. The use of Doppler imaging and the resistive index in patients with † AKI will be reviewed with attention to its use for (1) predicting the development of AKI, (2) predicting the Department of 3 Radiology and prognosis of AKI, and ( ) distinguishing prerenal azotemia from intrinsic AKI. Finally, pediatric considerations in §Department of Internal the use of ultrasonography in AKI will be reviewed. Medicine and Clin J Am Soc Nephrol 9: 382–394, 2014. doi: 10.2215/CJN.04840513 Pediatrics, Nephrology, University of Colorado Denver, Denver, Colorado; and Introduction structures on ultrasonography images. The renal cap- ‡Department of Renal ultrasonography is typically the most appro- sule consists of thin fibrous tissue, which is next to Radiology, University of priate and useful radiologic test in the evaluation of fat, and thus the kidney often appears to be surroun- Alabama at Birmingham, patients with AKI (1). In this report, we review the ded by a very bright rim on ultrasonography when Birmingham, Alabama interpretation of Doppler ultrasonography in adult there is a difference of acoustic impedance relative to and pediatric patients with AKI, with attention to the adjacent tissues. Solid organs, such as the liver Correspondence: its most appropriate uses, which include (1) the as- and spleen, have intermediate echogenicity, and the Dr. Sarah Faubel, sessment of intrinsic causes of AKI, (2) distinguishing kidney parenchyma, consisting of the cortex and me- Division of Nephrology, acute from chronic kidney diseases, and (3)detection University of Colorado dulla, is normally isoechoic (equal in brightness) or Denver, Denver of obstruction. hypoechoic (darker) compared with the normal liver Veterans Administration (2–4) or normal spleen. Thus, liver and spleen echo- Medical Center, 12700 East 19th Avenue, Box Use of Specific Parameters Obtained from genicity must be normal for comparison to be valid; fi C281, Aurora, CO Ultrasonography and Their Interpretation in particular, fatty in ltration of the liver can increase 80045. Email: sarah. Echoes and Echogenicity its echogenicity, making evaluation of the echogenic- [email protected] Proper interpretation of ultrasonography images ity of the right kidney more difficult. The cortex and depends on a basic understanding of how ultraso- medulla of the kidney generally have the same echo- nography images are generated. For diagnostic ultraso- genicity, although the medulla may be slightly darker nography, high-frequency sound waves are generated (5,6); both kidneys should have similar echogenicity and received by the ultrasonography transducer, which to each other. The renal sinus in the center of the is placed on the skin. Returning sound waves (echoes) kidney contains fibro-fatty tissue and thus appears are processed by a computer and displayed on a com- very bright relative to the kidney parenchyma. Bland puter screen. A gray-scale image is produced when the fluid (e.g., simple cysts), urine, and blood are an- ultrasonography machine operates in B-mode, or bright- echoic (black); therefore, the medullary pyramids, ness mode, in which returning echoes are represented which contain urine in parallel tubules, appear as as bright dots; the brightness of the dots represents the dark pools between the cortex and renal sinus. (See strength of the reflected echoes. Echogenicity, therefore, Figure 1 for the normal echogenic appearance of the refers to how bright or dark something appears in the capsule, parenchyma, medullary pyramids, and cen- gray-scale image; the brighter something appears, the tral renal sinus.) Blood clots in the urinary space will more echogenic it is. With regard to the kidney, echo- appear echogenic compared with the surrounding genicity generally refers to how bright or dark the kidney fluid; relative to the renal parenchyma, an acute clot parenchyma appears in comparison to the liver. is hypoechoic, while subacute and chronic clots are Normally, something that reflects most of the sound echogenic (brighter than renal parenchyma). waves back will appear the brightest (i.e., white); for What Is the Significance of Echogenicity in AKI example, fat and fibrous tissue are very echogenic and Other Kidney Diseases? Increased echogenicity and are therefore some of the brightest-appearing of the kidney parenchyma results from the increased

382 Copyright © 2014 by the American Society of Nephrology www.cjasn.org Vol 9 February, 2014 Clin J Am Soc Nephrol 9: 382–394, February, 2014 Use of Ultrasonography in Patients with AKI, Faubel et al. 383

Figure 1. | Grayscale ultrasonographic image demonstrating normal kidney size and echogenicity. (A) Grayscale longitudinal ultrasono- graphic image of a normal right kidney. The kidney is 11.2 cm long and surrounded by the bright rim of renal capsule (yellow arrow) around the parenchyma. The normal parenchyma (red line) forms a thick darker rim around the central bright (echogenic) sinus. Normal renal parenchyma is similar (isoechoic) or slightly darker (hypoechoic) compared with liver and includes the cortex and medulla. The thickness of the renal cortex is measured from the outer border of the medullary pyramids (yellow line) or from the arcuate arteries to the renal capsule. The medullary pyramids (white arrow) contain fluid in parallel tubules, which is anechoic (black) and appear as regularly spaced dark pools at the inner margin of the parenchyma (arrow). Because fat is echogenic, the central renal sinus appears bright. (B) Grayscale transverse ultrasonographic image of normal right kidney showing normal width (5.2 cm) and height (3.4 cm, anterior/posterior measurement) and appearance. (C) Grayscale longitudinal ultrasonographic image of normal right kidney next to a hyperechoic-appearing liver that has steatosis (because fat is echo- genic, the accumulation of fat increases the liver echogenicity/brightness). LNG, longitudinal view; MID, midline; RK, right kidney; TRV, transverse. presence of material that can reflect sound waves back, thus syndrome, complications of pregnancy (e.g., eclampsia), or increasing its brightness on the ultrasonography image. sepsis, which results in necrosis of tubular cells of the cortex; Because fibrous tissue (e.g., glomerulosclerosis, interstitial fi- the necrotic cells and resultant increase in interstitial fluid brosis) increases echogenicity, CKD is typically associated cause the decrease in cortical echogenicity (11). with increased echogenicity. Inflammatory infiltrates may Although clinically relevant kidney diseases may be present explain the increased echogenicity that occurs with acute in- without changes in echogenicity, if increased parenchymal terstitial nephritis and GN (7). Proteinaceous casts are echogenicity is noted (echogenicity is greater than a normal thought to cause the increased echogenicity associated liver) it is usually abnormal (except in neonates). For ex- with acute tubular necrosis (ATN) (8). Calcium deposits ample, increased echogenicity was reported to have a 96% and stones are very echogenic; thus, medullary nephrocalci- specificity (and 67% positive predictive value) for the presence nosis is characterized by increased medullary echogenicity of parenchymal (3). and a relatively normal-appearing cortex (Figure 2). Several Use of Increased Echogenicity to Distinguish AKI from renal diseases are associated with medullary , CKD. Increased echogenicity may occur in AKI or CKD and including medullary sponge kidney, hyperparathyroidism, re- cannot be used to reliably distinguish between the two. It is nal tubular acidosis, and vitamin D toxicity (9,10). Other kid- important to recognize, however, that in patients with CKD, ney diseases that have been associated with a hyperechoic it is unusual for kidney echogenicity to be less than that of the medulla include sickle cell disease and gout (9). liver. In one study, for example, only 11% of patients with Cortical necrosis is a rare cause of AKI that is classically CKD (serum creatinine, 8 mg/dl) had kidney echogenicity characterized by a dark, hypoechogenic renal cortex on ultra- that was less than liver echogenicity (2); of note, 30% of sonography. Cortical necrosis is a consequence of severe patients with AKI had kidney echogenicity that was less ischemia due to vascular abnormalities such as hemolytic-uremic than liver echogenicity. Furthermore, when ultrasonography 384 Clinical Journal of the American Society of Nephrology

Figure 2. | Hyperechoic (bright) medulla from medullary nephrocalcinosis. Several kidney diseases may be associated with a hyperechoic medulla, including medullary nephrocalcinosis, sickle cell diseases, and gout. The midline longitudinal image of the right kidney (A) and left kidney (B) demonstrate hyperechoic (bright) medulla (yellow arrow) in a 35-year-old woman with medullary calcinosis. (C) Axial noncontrast computed tomographic image of the same patient demonstrates calcification in medullary pyramids of both kidneys (black arrow). LK, left kidney; LO, long axis; MID, midline.

Figure 3. | Grayscale ultrasonographic image and resistive index (RI) in severe ischemic acute tubular necrosis. (A) Grayscale ultrasono- graphic image demonstrates normal renal length (11.7 cm), mild increased parenchymal echogenicity, and increased parenchymal thickness, and (B) Doppler imaging demonstrates very high RI (0.95) in a 21-year-old woman with severe ischemic acute tubular necrosis who required hemodialysis for 3 weeks. The patient eventually recovered normal kidney function. (Note: RI was determined in the renal artery near the segmental branch.) EVD, end diastolic velocity; L, left; PSV, peak systolic velocity; RenA, renal artery; RenA TS, renal artery time slope (acceleration time). characteristics were directly compared with renal histopa- that ischemic ATN might be characterized by normal thology, the combination of small kidneys and increased or reduced echogenicity (presumably from edema), while cortical echogenicity correlated very well with chronic, un- nephrotoxic ATN was characterized by increased echogeni- treatable kidney disease (12). It should be noted, however, city (13). Additional studies did not support this conclu- that diabetic kidney disease is one cause of CKD that may be sion, and it is now clear that increased echogenicity may associated with normal kidney echogenecity. also occur with ischemic ATN (2) (see Figure 3A). Increased Use of Echogenicity to Distinguish among Different echogenicity has been observed in several forms of AKI, Causes of AKI. Many studies have attempted to determine including acute interstitial nephritis (possibly from in- whether echogenicity might be useful to distinguish among creased inflammatory infiltrate), GN (possibly from vas- different forms of AKI. For example, it was originally reported cular changes), multiple myeloma (Figure 4), HIV Clin J Am Soc Nephrol 9: 382–394, February, 2014 Use of Ultrasonography in Patients with AKI, Faubel et al. 385

measurement of kidney size because it is simple to obtain and minimally affected by interobserver variability (15). Kidney length is useful in the assessment of patient with AKI and may help distinguish AKI from CKD. Kidney length to distinguish between AKI and CKD has been prospectively evaluated; in a study of 127 patients with creatinine.3.0 mg/dl, right kidney length was 11.261.4 cm among those with AKI and significantly shorter in pa- tients with CKD at 9.061.5 cm (2). Thus, small kidneys suggest the diagnosis of CKD; however, normal or in- creased kidney length may occur in either AKI or CKD. Large kidneys in AKI may result from infiltrative diseases (e.g., multiple myeloma, amyloidosis, lymphoma), acute parenchymal disorders due to edema and inflammation (e.g., acute GN [Figure 5, A and C], acute interstitial ne- Figure 4. | AKI in a patient with multiple myeloma. Grayscale lon- gitudinal ultrasonographic image of the right kidney demonstrates phritis), and renal vein thrombosis due to obstruction of fl abnormal bright renal parenchyma in a 39-year-old woman with blood ow and subsequent edema. multiple myeloma and AKI. Because kidney length is especially important in dis- tinguishing AKI from CKD, a clear understanding of nephropathy, and obstruction (6,14). Decreased echogenic- “normal” kidney length is important. Studies of kidney ity may occur with renal infarcts and renal lymphoma (14). length have revealed the following: (1)normalkidney Overall, changes in kidney echogenicity alone are unlikely length is approximately 11 cm, with a normal range of to be useful for distinguishing among the different causes 10–12 cm; (2) the left kidney is longer than the right by of AKI; however, in conjunction with kidney length and 0.3 cm; (3) women have smaller kidneys than men by symptoms, certain disease may be more likely than others, 0.5 cm; (4)kidneysizes,10 cm are unusual in people as summarized in Table 1. younger than age 60 years, (5) kidney length decreases with age beginning at age 60 (see Table 2) (16,17). Thus, Kidney Size 9.5-cm kidneys probably represent CKD in a 30-year-old Although renal volume is the most accurate measure manbutmaybeexpectedinan80-year-oldwoman.It of renal size, kidney length is the most clinically useful remains unknown whether kidney length “normally”

Table 1. Differential diagnosis of kidney diseases based on kidney size, echogenicity, and symptoms

Differential Diagnosis of Kidney Diseases

Normal echogenicity with normal or increased Normal or increased echogenicity with increased kidney size kidney size and reduced kidney function Early diabetic nephropathy GN Vasculitis Normal echogenicity with increased kidney size Tubulointerstitial disease (e.g., acute interstitial and normal kidney function nephritis) Steroid use Amyloid Obesity Multiple myeloma Tall stature HIV nephropathy Acromegaly Pre-eclampsia Diabetes

Asymptomatic, unilateral increase in kidney size Increased medullary echogenicity with normal cortex Hypertrophy from decreased function of other kidney Medullary nephrocalcinosis Renal duplication anomaly Tamm Horsfall protein in tubules Lymphoma/leukemia (usually affects both kidneys) Urate nephropathy Sickle cell disease Symptomatic, unilateral increase in kidney size Sjögren syndrome Medullary sponge kidney Acute vascular insult (e.g., renal vein thrombosis) Urinary tract obstruction Decreased cortical echogenicity (i.e.,darkcortex) Acute cortical necrosis Edema

Kidney diseases may have a particular appearance based on kidney length, echogenicity, and symptoms as listed in the table above. Although baseline kidney size is often not known, if a change in kidney size .1 cm is detected relative to a prior study, it is unlikely to be due to interobserver variability (6). 386 Clinical Journal of the American Society of Nephrology

Figure 5. | Grayscale ultrasonographic image and resistive index in glomerular diseases. Patients with glomerular disease are classically described as having increased kidney size, with normal or increased parenchymal echogenicity, and normal resistive index. (A) Grayscale ultrasonographic image of LK demonstrates increased kidney size (13.1 cm) and normal parenchymal echogenicity and (B) Doppler image demonstrates resistive index of 0.51 in a 50-year-old man with biopsy-proven minimal-change disease. (C) Grayscale ultrasonographic image of RK demonstrating increased kidney size (13.6 cm) and normal parenchymal echogenicity, and (D) normal resistive index (0.63) in 57-year- old man with rapidly progressive GN and biopsy-certain necrotizing and crescentic GN from a pauci-immune GN; creatinine was 4.3 mg/dl at time of biopsy. decreases with aging or whether the decrease in kidney relative differences in kidney sizes between men and women length represents the development of CKD. Kidney length are eliminated. In one study (18), kidney size varied by also varies with height; when adjusted for height, the weight and height according to the following formula:

Table 2. Normal kidney length (in cm) in adults based on age (in years)

Age Kidney Length 30 yr 40 yr 50 yr 60 yr 70 yr

Left median kidney length 11.5 11.3 11.3 11.1 10.5 10th percentile 10.4 10.3 10.2 10.0 9.4 90th percentile 12.8 12.3 12.5 12.2 12.0 Right median kidney length 11.1 11.2 11.0 10.8 10.4 10th percentile 10.1 10.0 10.0 9.5 9.1 90th percentile 12.4 12.3 12.2 12.0 11.8

Kidney length was determined in a random population of study of 665 adult volunteers without ultrasonographic evidence of kidney disease; median left and right kidney size with 10th and 90th percentiles were reported according to age (16). Clin J Am Soc Nephrol 9: 382–394, February, 2014 Use of Ultrasonography in Patients with AKI, Faubel et al. 387

Figure 6. | Grayscale ultrasonographic image in CKD. (A) Grayscale longitudinal ultrasonographic image of a 67-year-old man with stage 4 CKD (creatinine, 4.0 mg/dl) and long-standing hypertension. Kidney size is small (8.78 cm) and renal parenchyma is thin. The finding of small kidneys or a thin parenchyma is diagnostic of CKD. (B) Grayscale longitudinal ultrasonographic image of RK demonstrates kidney size of 11.4 cm, abnormal bright (diffusely increased echogenicity) renal parenchyma, although parenchymal thickness is normal, in a 32-year-old man with CKD (creatinine 3.3 mg/dl) due to severe poorly controlled hypertension (BP, 230/130 mmHg at time of examination).

Figure 7. | Doppler imaging and resistive index. (A) Normal color and spectral Doppler ultrasonogram of the right main renal artery (MRA) demonstrates normal peak systolic velocity (98.5 cm/sec), resistive index (0.67), and acceleration time (32 milliseconds). (B) Normal color and spectral Doppler ultrasonogram of the right superior segmental renal artery (SEG ART SUP) demonstrates normal resistive index (0.68). (C) Spectral Doppler image of left inferior segmental renal artery demonstrates an abnormally high resistive index of 0.76 in a 39-year-old woman with multiple myeloma and AKI. Resistive index is determined by the following formula: (peak systolic velocity 2 end diastolic velocity)/(peak systolic velocity); in A and B, peak systolic velocity is indicated by the long yellow arrows, and end diastolic velocity is indicated by the short purple arrows. AO, aorta.

kidney size ðmmÞ5 49:18 1 ð0:21 3 weight in kilogramsÞ Doppler Ultrasonography and Resistive Index Doppler imaging is used to assess the velocity of blood 1 ð0:27 3 height in centimetersÞ: flow. Blood velocity is determined by computer interpre- In addition to kidney length, assessment of the kidney tation of the magnitude of the frequency shift of the parenchyma thickness is also useful to distinguish AKI returning ultrasonography echoes of moving red blood from CKD. The kidney parenchyma includes the cortex cells and the Doppler equation. Resistive index (RI) is (containing glomeruli) and the medulla; the cortex is probably the most commonly used variable in Doppler normally about 1 cm (17,19), and the entire parenchyma imaging to evaluate blood flow in vessels. RI is very is normally about 1.5 cm (16). Thinning of the renal paren- reproducible (20) when performed by a trained imager chyma or cortex commonly occurs in CKD and is a useful because the value is calculated as a ratio of two velocities measure to identify CKD if it is present (Figure 6); normal obtained from the same transducer angle (in contrast to cortical thickness may occur in acute or chronic kidney the importance of angle to assess renal artery stenosis in disease. In one study, mean parenchymal thickness was the main renal artery). In the kidney, RI is determined by 10.760.4 mm in CKD versus 13.860.3 mm in AKI and assessing systolic and diastolic blood velocity in the seg- 13.661 mm in healthy controls (2). Measurement of the mental arteries and applying the following formula: cortical thickness can be affected by technique because ðPeak systolic velocity end diastolic velocityÞ the cortex may be thicker at the poles or in the region = : of a column of Bertin. peak systolic velocity 388 Clinical Journal of the American Society of Nephrology

Figure 8. | AKI due to hepatorenal syndrome. (A and C) Grayscale longitudinal ultrasonographic images of the right and left kidneys dem- onstrates normal renal parenchyma in a 51-year-old man with cirrhosis, ascites, end-stage liver disease due to hepatitis C, and AKI due to hepatorenal syndrome (serum creatinine, 2.5 mg/dl; low urinary sodium ,10 mEq/L). (B and D) Spectral Doppler ultrasonograms of segmental renal artery in the same patient demonstrates an increased resistive index of 0.74 in the right kidney and 0.77 in the left kidney. SEG ART MID, middle segmental artery.

Because RI is a calculation of the relationship between with widespread atherosclerosis (24) or reduced vascular systole and diastole, it is an indicator of the resistance to compliance in general (as in elderly patients [20]), the renal flow within the kidney. For example, if the resistive index is RI may be increased even with normal kidney function. 0.9, then there is a large difference (i.e., a 90% drop) be- The influence of these factors needs to be considered to tween systolic and diastolic blood flow that reflects an in- properly interpret renal RI; indeed, the potential utility creased resistance to blood flow during diastole. If the RI is of RI in AKI (discussed below) and kidney disease in gen- low, then renal vascular resistance is low. Normal RI is eral rests on a clear understanding of the renal and non- approximately 0.6 (ranging between 0.56 and 0.66), and renal factors that affect RI (25). in a study of 120 kidneys, only 3% had a mean RI.0.70 Use of RI in AKI. RI may increase in several causes of (20) (Figure 7A). Increased RI can occur in both CKD and AKI (Figures 3B and Figures 7B), including obstruction, AKI, and, in general, higher levels of RI are associated acute rejection, hepatorenal syndrome (Figure 8B), and with worse renal parenchymal damage and worse out- sepsis; the RI remains normal in prerenal azotemia and come. In patients with CKD, for example, an RI.0.70 glomerular diseases (Figure 5, B and D). Studies suggest was independently associated with worsening kidney that RI may be a useful tool for predicting AKI, distin- function in patients with CKD at both 2 and 4 years of guishing ATN (or other parenchymal diseases) from pre- follow-up (21,22). renal azotemia, and predicting severity in AKI as Several factors can influence RI independent of renal summarized in Table 3. Three studies (26–28) have exam- disease, including heart rate, vessel wall compliance, and ined the utility of RI to predict AKI; in these studies, RIs of systemic vascular resistance. Bradycardia increases the RI 0.74, 0.74, and 0.71 were found to be useful cut-points to because there is more time for the diastolic flow to decrease; predict AKI 1–5 days after the RI measurement in patients on the other hand, tachycardia does not allow the diastolic after cardiac bypass requiring surgery, with septic shock, flow to fully decrease, thus lowering the RI (23). In patients or in the intensive care unit (ICU) for trauma or sepsis, Clin J Am Soc Nephrol 9: 382–394, February, 2014 Use of Ultrasonography in Patients with AKI, Faubel et al. 389

Table 3. Summary of studies examining the use of resistive index (RI) in AKI

Study (Reference) Renal RI/Group Study Notes

Healthy volunteers (20) 0.6060.07/Normal Predicting AKI post- 0.6860.06/No AKI 1–5 d later Single-center, prospective, n565 CPB (26) 0.7760.08/AKI without RRT RI was determined immediately after CPB 1–5 d later 0.8460.03/AKI requiring RRT Presence of AKI was assessed on days 1–5 1–5 d later An RI.0.74 had an AUC of 0.91 to predict AKI with 85% sensitivity and 94% specificity Predicting AKI in septic 0.6860.08/No AKI 5 d later Single-center, prospective, n535 shock (27) 0.7760.08/AKI 5 d later RI was obtained within 24 h of ICU admission Presence of AKI was assessed on day 5 AKI was defined as RIFLE stage 2 or greater (i.e., doubling of serum creatinine or greater) An RI.0.74 predicted AKI with 78% sensitivity and 77% specificity Predicting AKI in the 0.6660.08/No AKI 3 d later Single-center, prospective, n558 ICU (28) (sepsis and 0.8060.08/AKI 3 d later RI was obtained within 12 h of ICU trauma) admission Presence of AKI was assessed on day 3 AKI was defined as stage 2 AKIN or greater (i.e., doubling of serum creatinine or greater) An RI of 0.71 predicted AKI with an AUC of 0.91 Identifying prerenal 0.6760.90/Prerenal azotemia Single-center, n591 azotemia (29) 0.7460.13/Non-ATN AKI An RI$0.75 occurred in 91% of patients with (mostly HRS) ATN and 20% of patients with prerenal 0.856 0.60/ATN azotemia Identifying prerenal 0.7660.06/Prerenal azotemia Single-center, n550 azotemia (30) 0.8260.07/ATN An RI$0.75 had 91.3% sensitivity and 85.2% specificity to distinguish ATN from prerenal azotemia Identifying prerenal 0.52–0.71/Prerenal azotemia Single-center, n540 azotemia/assessing 0.77–1.0/ATN Decreasing RI predicted renal recovery severity (31) Assessing severity (57) 0.71 (0.62–0.77)/Transient AKI Single-center, n551 0.82 (0.80–0.89)/Persistent AKI Persistent AKI was defined as AKI for .3d An RI.0.795 had 82% sensitivity and 92% specificity for persistent AKI

Values are expressed as mean 6 SD. Numbers in parentheses are references. CPB, cardiopulmonary bypass; RRT, renal replacement therapy; AUC, area under the curve; ICU, intensive care unit; RIFLE, risk, injury, failure, loss, and end-stage kidney disease; AKIN, Network; ATN, acute tubular necrosis; HRS, hepatorenal syndrome.

respectively; patients who did not develop AKI had initial Use of Ultrasonography in Patients with AKI to RIs of 0.68, 0.68, and 0.66, respectively. In studies of RI in Evaluate for Obstruction prerenal azotemia versus intrinsic AKI (29–31), an RI$0.75 Ultrasonography is the modality of choice to evaluate correlated well with the diagnosis of ATN, while prerenal for the presence of obstruction, which accounts for 1%–3% azotemia was typically associated with an RI,0.71. Fi- of cases of AKI in the ICU (32–34), approximately 15% nally, RI may be able to predict recovery of AKI (Figure of non-ICU AKI cases (34), and approximately 10% of 3B); patients with transient AKI had a median RI of 0.71, community-acquired AKI cases (35). Obstruction is due while patients with persistent AKI (lasting .3 days) had a to blockage anywhere in the , which inter- median RI of 0.82 (11). Given the keen interest in the de- feres with proper urine flow; thus, clinically meaningful velopment of biomarkers for early AKI, the clinical diffi- obstruction is typically associated with culty in distinguishing prerenal azotemia from intrinsic (dilatation of the urinary collecting system from the accu- AKI, and the need for markers of severity of AKI, the mulation of urine) as shown in Figures 9 and 10. In fact, role of RI in these setting merits further investigation approximately 95% of patients with obstruction will have and validation in larger clinical trials. hydronephrosis on ultrasonography (36); sensitivity 390 Clinical Journal of the American Society of Nephrology

Figure 9. | Grayscale ultrasonographic images demonstrating varying degrees of hydronephrosis. Grayscale longitudinal ultrasonographic image of the right kidney obtained at different time periods in the same patient demonstrates mild (A), moderate (B), and severe (C) hydro- nephrosis in a 59-year-old man with metastatic prostate cancer and creatinine level of 15 mg/dl. Grayscale longitudinal ultrasonography of both kidneys demonstrates severe right (D) and severe left (E) hydronephrosis in a 54-year-old man with AKI (creatinine increase of 1.2– 1.5 mg/dl), benign prostatic hypertrophy, and acute urinary retention. MED, medial. approaches 100% in patients with moderate to severe hy- presence of any of the following: (1) nonblack race, (2) dronephrosis (1). False-negative findings (obstruction history of recurrent urinary tract infections (three in pre- without hydronephrosis) can occur in the following set- vious year), (3) diagnosis consistent with possible obstruc- tings: retroperitoneal fibrosis/retroperitoneal tumors tion (benign prostatic hyperplasia, abdominal/pelvic (due to the inability of the collecting system to dilate), cancer, neurogenic bladder, single functional kidney, or prerenal states/volume depletion, and early obstruction previous pelvic surgery), (4) no congestive heart failure, (too early for dilatation to occur) (37). False-positive re- (5) no history of prerenal AKI, pressors, sepsis, or (6)no sults (hydronephrosis without obstruction) may occur in exposure to nephrotoxins. Four points are awarded for a thefollowingsettings:pregnancy,vesicoureteralreflux, history of hydronephrosis. Patients are divided into low, after relief of obstruction, megacystis- syn- medium, and high risk if they had #2 points, 3 points, or drome, full bladder, , and brisk di- $4 points, respectively. The prevalence of hydronephrosis uresis (as in nephrogenic diabetes insipidus) (6,38). Thus, was 3% in the low-risk group, 10.7% in the medium-risk when hydronephrosis is identified, tests to confirm the group, and 16.1% in the high-risk group. Thus, 2 points or presence of true obstruction may need to be performed less helped predict a negative ultrasonography result for (e.g., diuretic renography, Doppler imaging for ureteral hydronephrosis 97% of the time. jets [Figure 11]). The appropriate use of ultrasonography for the evalu- Studies suggest that clinical suspicion is a useful pre- ation of AKI, with or without clinical suspicion of obstruc- dictor of the presence of obstruction. In a retrospective tion, has been vigorously debated. We and others (41) analysis of 60 patients referred to ultrasonography for an suggest that renal ultrasonography is particularly impor- increased creatinine level, Gottlieb et al. found that all of tant in the evaluation of AKI if the diagnosis is unclear or the patients with hydronephrosis had a clinical history the clinical course is not as expected. It is useful to note suggestive of obstruction (39). Extending these observa- that the American College of Radiology (ACR) Appropri- tions, Licurse et al. examined whether clinical measures ateness Criteria rating for the use of ultrasonography in could indeed be used to risk-stratify patients for likelihood AKI is a 9, the highest rating, indicating that its use in AKI of obstruction (40). Although not validated in other is highly appropriate. The ACR Appropriateness Criteria centers, a clinical decision rule was developed and inter- are a compilation of evidence-based recommendations to nally validated. In that study, 7 of 36 clinical variables aid in the selection of radiologic imaging for a variety of med- were important in the assessment of obstruction, and a ical conditions. The web-based tool is available at http:// point system was devised: One point is awarded for the www.acr.org/Quality-Safety/Appropriateness-Criteria Clin J Am Soc Nephrol 9: 382–394, February, 2014 Use of Ultrasonography in Patients with AKI, Faubel et al. 391

Figure 10. | Grayscale ultrasonographic images of hydronephrosis due to obstructing stones. Grayscale longitudinal ultrasonographic image of the right kidney demonstrates hydronephrosis (A) with a dilated (B) (red arrow) due to an 8-mm hyperechoic, obstructing stone (yellow arrow) in the proximal ureter in a 26-year-old woman with right flank pain. (C) Grayscale longitudinal ultrasonographic image of the left kidney demonstrates hydronephrosis containing complex fluid due to a large, echogenic, staghorn calculus (blue arrows) in the renal pelvis causing pyonephrosis in a 60-year-old man who presented with sepsis; (D) color Doppler ultrasonogram does not demonstrate flow, confirming that it is a dilated collecting system containing urine and not blood vessels in the central renal sinus (urine and blood are both anechoic [black]; color Doppler imaging can be used to distinguish urine [no flow] from blood in vessels [flow is present]).

(orsimplydoawebsearchfor“appropriateness criteria”); the the setting of renal failure. Several caveats must be noted site is searchable for a wide variety of topics, such as renal with respect to pediatric renal ultrasonography, however. masses or abdominal pain. The appropriateness of imag- Normal renal length and volume vary with body size, and ing techniques (e.g., ultrasonography and magnetic reso- individual imaging results must be compared with known nance imaging) are ranked on a scale from 1 to 9 with the norms (42–45) (Table 4). More recent data suggest that re- following interpretations: 1, 2, 3: usually not appropriate; nal length is related to numerous individual variables, in- 4, 5, 6: may be appropriate; 7, 8, 9: usually appropriate. cludingage,sex,race,height,andweight(42).The The recommendations regarding ultrasonography (and appearance of the normal neonatal kidney by ultrasonog- other imaging techniques) for AKI may be found using raphy differs significantly from that of older children and the search term “acute renal failure.” (Please note that adults, with relatively hyperechoic cortex and hypoechoic the criteria for AKI are being updated with new recom- pyramids, little sinus fat, and frequent fetal lobulation (46). mendations anticipated soon). The echogenicity of the renal cortex becomes more hypo- echoic than liver by approximately 4–6 months of age. In Utility of Ultrasonography in Pediatric AKI younger children, prominent renal pyramids are easily Ultrasonography is a critical imaging tool in the evalu- mistaken for dilated calices or renal cysts. Norms for RI ation of AKI in children because it can help to exclude are age dependent, with the highest values noted at birth underlying chronic and/or congenital renal conditions, and increased normal values in preterm (0.8–0.9) versus requires no radiation exposure, and is easily performed in term infants. Normal RI decreases during childhood, children of all ages. Alternatively, computed reaching typical adult values of ,0.7 by 4–5 years of age and magnetic resonance imaging often require sedation in (47). This is in large part due to the normal decrease in children and are associated with concerns similar to those renal vascular resistance and increase in systemic BP that in adults with respect to contrast/gadolinium exposure in occur postnatally. 392 Clinical Journal of the American Society of Nephrology

Figure 11. | Hydronephrosis without functional obstruction. Grayscale and color Doppler ultrasonogram of a 59-year-old woman with right flank pain demonstrate mild right hydronephrosis (A) and hydroureter (yellow arrow) (B) ureteric jet (C) (white arrow) in the bladder. No calculus was seen on computed tomography of the kidneys, , and bladder done at the same time. Thus, this likely represents a recently passed calculus or vesico-ureteric reflux and hydronephrosis without functional obstruction is present. (C) The utility of Doppler imaging to assess for functional obstruction by assessing the ureteric jet. When the bolus of urine being transmitted through the ureter reaches the terminal portion, it is ejected forcefully into the bladder through the vesicoureteric junction. This creates a jet of urine that can be seen within the urinary bladder on grayscale and color Doppler ultrasonography (white arrow; jet appears red). LNG, longitudinal; MED, medial.

As in adults, an important function of sonographic during acute illness does not necessarily signify AKI. Renal imaging in pediatric renal failure is to exclude CKD. ultrasonography is valuable for detecting previously un- Because most symptoms of pediatric CKD are nonspecific, diagnosed chronic renal conditions, such as congenital detection of an increased serum creatinine concentration hypoplasia/dysplasia, cystic disease, or urinary tract dilation

Table 4. Normal values for renal variables by age

Mean Serum Mean Estimated GFR Mean Kidney Resistive Index Age Creatinine (mg/dl) (58) (ml/min per 1.73 m2)(58) Length (cm) (44) (47,59,60)

Preterm neonate 0.9 11 Depends on 0.8–0.9 gestational age (61,62) Term neonate 0.5 39 4.5 0.7–0.8 1 yr 0.3 103 6.6 0.7–0.8 5 yr 0.4 127 8.1 ,0.7 10 yr 0.6 127 9.2 ,0.7 15 yr 0.9 127 10.9 ,0.7

Numbers in parentheses are references. Clin J Am Soc Nephrol 9: 382–394, February, 2014 Use of Ultrasonography in Patients with AKI, Faubel et al. 393

suggestive of underlying obstructive uropathy. For example, Conclusion hypoplastic/dysplastic kidneys may be small with altered In summary, ultrasonography is a useful tool in the echotexture and reduced corticomedullary differentiation. evaluation of adult and pediatric patients with AKI for Autosomal recessive polycystic kidney is associated with assessing obstruction, parenchymal evaluation, and dis- symmetrically enlarged hyperechoic kidneys with poor tinguishing acute from chronic kidney diseases. With better corticomedullary differentiation. Small scarred kidneys are understanding of the pathogenesis of certain causes of AKI, observed in a variety of conditions causing chronic renal it is anticipated that renal ultrasonography may become an failure/ESRD. even more important tool in the assessment, management, Renal ultrasonography also has utility in the differenti- and treatment of patients with AKI. ation of prerenal, intrinsic, and postrenal causes of AKI. 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