The Kidney: Diffuse Parenchymal Abnormalities

Small, Scarred Kidney

Disease processes producing small kidneys fall into several categories. Is the kidney smooth or irregularly contoured as a result of parenchymal scarring? If the kidney is scarred or if both kidneys are small and scarred, then several other factors must be considered. Where are the scars located in relation to the calyces, and are the calyces normal? Small, scarred kidneys usually result from ischemic disease caused by small-vessel occlusions in the kidney, from reflux nephropathy, or from analgesic nephropathy ( Box 4-1 ). Renal scarring resulting from reflux is often more pronounced in one kidney. Scarring caused by small-vessel disease and analgesic nephropathy is typically bilateral. Occlusion of interlobar arteries usually results from advanced atherosclerosis, and small-vessel involvement may be seen in patients with diabetes, hemoglobinopathy, or collagen vascular diseases. Interlobar arteries are radially arrayed vessels extending between renal lobules. Each of these lobules has one or more calyces in its center. Parenchymal scarring caused by occlusion of the interlobar arteries results in thinning of the parenchyma between calyces. The parenchyma directly atop the calyx is of normal thickness. In addition, the calyces receive their arterial supply from a separate network of vessels derived from the main renal artery and the ureteric arteries. Therefore occlusion of interlobar arteries does not lead to structural changes in the calyces. As a result, small kidneys with scars centered between normal calyces indicate renal atrophy due to remote interlobar artery occlusions.

Alternatively, bilateral small kidneys with scars centered over all calyces or with medullary calcifications indicate a diagnosis of analgesic nephropathy. Findings of papillary necrosis within the renal medulla and calyces are often present.

Reflux nephropathy, sometimes referred to as chronic atrophic pyelonephritis, is a major cause of atrophy with an irregular renal contour. Parenchymal scarring can be caused by reflux of either sterile or bacteria-laden urine. For scarring to develop, reflux must be chronic, and usually massive. The occurrence of this combination of factors is almost always limited to children. However, the kidney's structural changes are permanent and may first be detected during adulthood ( Fig. 4-1 ). Reflux confined to the calyces leads to calyceal blunting without overlying parenchymal atrophy. Atrophic parenchymal changes occur when reflux extends through the ducts of Bellini (the openings that drain urine from tubules in the renal medulla into the calyces) into the renal medulla. This process tends to follow a typical pattern. Previous work has demonstrated that the ducts of Bellini vary in their ability to prevent intrarenal reflux. Most of these ducts have openings that act as slitlike, flap valves that are quite effective in preventing parenchymal entry of urinary reflux from the calyx. Atrophy of the kidney overlying these areas occurs only after the long-standing, massive reflux overcomes this antireflux mechanism. Alternatively, some ducts of Bellini have circular openings that are less effective at inhibiting intraparenchymal reflux. Circular duct openings occur most commonly in compound calyces that are usually present in the polar regions of the kidney as described in Chapter 2 . This leads to an interesting radiographic pattern typical of reflux nephropathy. In most cases the first, and often the only, signs of reflux nephropathy occur in the upper and lower poles of the kidney ( Fig. 4-2 ), sparing the interpolar region. The parenchymal scars are broad based and centered atop the subtending calyx. In addition, the underlying calyx is abnormal. Because of parenchymal atrophy and chronic reflux, the calyx loses its normal concave shape and becomes club shaped with convex margins (see Fig. 4-2 ). Additional parenchymal contour irregularity may result from compensatory hypertrophy in the unaffected areas of the kidney. This can lead to exaggeration of the contour irregularities induced by reflux nephropathy. Although reflux nephropathy is usually unilateral, bilateral changes are not rare. In fact, severe reflux nephropathy is not an uncommon cause of irreversible renal insufficiency.

In summary, typical changes of reflux nephropathy include a small, scarred kidney with the scars centered atop an abnormal calyx. Scars develop first in, and may be limited to, the renal poles, but advanced cases may involve the kidney globally.

Unilateral Small, Smooth Kidney

The single most common cause of this imaging pattern is ischemic parenchymal injury resulting from chronic renal artery stenosis or occlusion ( Fig. 4-3 ). Other causes of a unilateral small, smooth kidney are chronic renal vein thrombosis (RVT), postobstructive atrophy, renal hypoplasia, previous renal trauma with subcapsular hematoma, and previous radiation therapy to the renal bed ( Box 4-2 ). Secondary radiographic features are very helpful in distinguishing among this group of abnormalities. On imaging studies (intravenous urography, enhanced CT, or MRI with gadolinium), findings suggestive of renal artery stenosis include a small, smooth kidney that exhibits delayed nephrographic progression and pyelographic opacification, and subsequent hyperdense pyelographic opacification ( Box 4-3 ). However, the calyces and ureter appear normal. In fact, the calyces may appear very delicate because of limited distention from decreased urine output by the ischemic kidney. Because the contrast material is delivered through the bloodstream, there is usually a delay in nephrographic opacification owing to the reduced inflow through the abnormal renal artery. Reduced blood flow may also cause a delay in opacification of the collecting system because less contrast is delivered to the involved kidney, and there is decreased perfusion pressure propelling the contrast material through the nephron. When the time required for passage of contrast media in the tubules is prolonged, reabsorption of water increases, which in turn leads to higher concentration of contrast medium in the tubules of the affected kidney compared with the normally perfused kidney. This delay, combined with the property of most intravascular contrast agents that once excreted into the tubules they cannot be reabsorbed through the tubular epithelium, leads to development of the hyperdense pyelogram. At imaging, this leads to a higher density of contrast medium in the ischemic kidney than in the normal kidney in the pyelographic phase. These alterations in flow are identifiable on most enhanced imaging examinations ( Fig. 4-4 ).

Another imaging sign, sometimes identified in association with renal artery stenosis, is impressions on the ureter and renal pelvis because of enlarged collateral ureteric arteries ( notching ; Fig. 4-5 ). These arteries are recruited to provide additional blood supply to the ischemic kidney. Ureteric vessels supplying the mid and lower ureter that originate from lumbar arteries and branches of the iliac artery form a network of anastomoses with renal pelvic and upper ureteric arterial branches arising from the main renal artery. The connection of the ureteric vessel network with the main renal artery is often distal to the stenosis because most stenoses occur at or near the ostium of the artery. Thus ureteric vessels can enlarge to help supply more blood to the ischemic kidney. The enlarged vessels or the impressions they create on the adjacent collecting system or ureter may be seen at imaging.

For patients with suspected renovascular hypertension it is unclear which of the following is the best screening examination: sonography, the radionuclide renogram augmented with captopril, or CT or MR angiography (MRA). A test used for screening the hypertensive population is renal sonography augmented with Doppler analysis of the renal arteries and intrarenal spectral waveforms ( Box 4-4 ). However, results for this test have been variable. Some institutions have a high detection rate of renal artery stenosis with this technique, whereas other reports indicate that this test is unreliable. It appears that in some centers, Doppler sonography may allow for a fairly high degree of accuracy in the detection of renal artery stenosis. Nowadays, detection of renal artery stenoses is often performed with CTA or MRA. Gadolinium-enhanced dynamic three-dimensional MRI produces detailed images of the renal arteries, which are satisfactory for diagnosing a significant renal artery stenosis. Applying only a standard dose of gadolinium for contrast avoids the use of a potential nephrotoxic agent in these patients, an advantage over catheter or CT angiography (CTA). Newer multislice CT scanners may be useful for accurate renal artery imaging with lower volumes of intravenous contrast medium than with older CT machines. This offers the promise of reducing the risk of nephrotoxicity for these focused examinations. Currently, confirmation and treatment of renal artery stenosis are best achieved using digital subtraction angiography. For patients with contraindications to the administration of intravascular contrast material, flow-sensitive MRI of the vessels or digital subtraction catheter angiography using carbon dioxide as an alternative contrast agent might be considered.

It is also important to differentiate between renal artery stenosis and ureteral obstruction because they share some features on imaging. Acute ureteral obstruction also leads to delayed development and progression of the nephrogram and pyelogram. However, an enlarged kidney, presence of hydroureteronephrosis and a dilute pyelogram, as well as symptoms of ureteral colic usually accompany ureteral obstruction ( Fig. 4-6 ).

Chronic RVT is another vascular cause of renal ischemia. If inadequate venous collaterals develop, a small ischemic kidney will result from chronic RVT. Chronic RVT can also lead to other radiographic features mimicking renal artery stenosis. These include delayed pyelogram, hyperdense pyelogram, and nondilated normal-appearing calyces and ureter. US with Doppler evaluation of the renal artery and vein often leads to the correct diagnosis. Noninvasive angiographic techniques, such as MRA and CTA, are the best techniques for the diagnosis of RVT.

The Page kidney is another name for renal atrophy resulting from a subcapsular hematoma. Because the renal capsule is rigid, a subcapsular hematoma exerts opposing hydraulic pressure on perfusion of the renal parenchyma. If untreated, this eventually leads to parenchymal ischemia and atrophy ( Fig. 4-7 ). The kidney usually maintains a near reniform shape, and the calyces appear normal. As with renal artery stenosis, hypertension often results from overstimulation of the renin-angiotensin system secondary to parenchymal ischemia. The key to this diagnosis is a clinical history of flank trauma. This can occur in deceleration injuries or falls, but can also be seen in young patients with sports-related injuries. These subcapsular hematomas may go unrecognized at the time of acute injury and may be identified incidentally during imaging at a later time for evaluation of hypertension or unrelated symptoms. In some cases the remnant of the subcapsular hematoma is visible with cross-sectional imaging. This confirms the diagnosis of Page kidney.

Radiation therapy that includes the renal bed can lead to parenchymal ischemia. The ischemia results from a small-vessel arteritis induced by the radiation, and this in turn causes parenchymal atrophy that may mimic other vascular causes of renal ischemia ( Fig. 4-8 ), including chronic RVT and renal artery stenosis. This is rarely seen with modern radiation therapy techniques, but should be considered in patients who have undergone radiation treatment for tumors in the region of the kidney. Other radiographic clues suggesting prior radiation therapy can sometimes be identified in the adjacent spine. These include osteonecrosis and resulting scoliosis.

An uncommon cause of a unilateral small and smooth kidney is postobstructive atrophy. This condition can be seen in patients who have experienced long-standing ureteral obstruction for any of a variety of causes. High-grade ureteral obstruction with sterile urine must persist for at least 3 weeks to lead to irreversible parenchymal atrophy. During the acute obstructive phase, the kidney is usually edematous, swollen, and distended, rather than atrophic. However, when long-standing obstruction is relieved, parenchymal atrophy becomes evident. Unlike reflux nephropathy, ureteral obstruction leads to increased pressure spread evenly throughout the renal parenchyma. Once the obstruction is relieved, some renal function may return but global atrophy and residual ectasia of the collecting system will be evident ( Fig. 4-9 ). Collecting system ectasia, with dilatation and residual clubbing of the calyces, distinguishes this entity from other causes of a unilateral small, smooth kidney. In many cases there will be a history of previous intervention to relieve the ureteral obstruction. In particular, postobstructive atrophy is often seen in patients with pelvic malignancies, including bladder and ureteral neoplasms. If these are surgically treated, or if the urinary stream is diverted after a significant period of ureteral obstruction, post­obstructive atrophy will be evident.

Finally, renal hypoplasia is a rare cause of a unilateral small, smooth kidney, which at imaging appears as a normal kidney with too few calyces. This entity is thought to result from underperfusion of the fetal kidney. The small kidney functions normally and has normal parenchymal thickness; however, by definition, there will be five or fewer calyces in the intrarenal collecting system. Although there are fewer calyces, they appear completely normal. No additional signs of abnormality, such as those seen with renal artery stenosis, are present with the hypoplastic kidney. Renal arteriography demonstrates a widely patent renal artery that is diminutive (in proportion to the diminutive functioning renal mass in the hypoplastic kidney). The artery is small owing to a small volume of renal parenchyma requiring arterial supply.

In summary, a unilateral small, smooth kidney with normal calyces is most likely due to renal artery stenosis. Additional radiographic signs of renal artery stenosis should be sought in this situation. A small, smooth kidney with associated collecting system ectasia and calyceal blunting suggests postobstructive atrophy. A normal small, smooth kidney that contains a complement of five or fewer calyces is likely to be a congenital hypoplastic kidney. Other entities with this pattern that should be considered are chronic RVT, Page kidney, and previous radiation therapy affecting the renal bed.

Bilateral Small, Smooth Kidneys

Significant bilateral renal atrophy is usually associated with renal insufficiency. Patients are generally imaged with US, nonenhanced CT, or MRI ( Fig. 4-10 ). Most cases of renal insufficiency are due to chronic medical renal disease of various etiologies, including diabetes, nephrosclerosis due to hypertension, chronic glomerulonephritis, bilateral renal artery stenosis, analgesic nephropathy, hereditary nephropathy, autoimmune diseases, or remote acute tubular necrosis. Evidence of renal artery stenosis may be obtained with noninvasive techniques such as Doppler US or MRA and can be confirmed with digital subtraction angiography, if treatment is contemplated. Other entities may require renal biopsy for a tissue diagnosis. In any case the atrophy is likely to be irreversible and, at best, renal function may be stabilized rather than improved.

One unique entity that may lead to this pattern is renal medullary cystic disease. The condition is usually seen in children who develop a salt-wasting nephropathy, but a subtype occurs in adults in whom renal insufficiency and salt-wasting nephropathy develop insidiously. In either case, the kidneys are usually small and contain numerous medullary cysts. There is no known treatment for this disease, which usually occurs sporadically, although some cases appear to be inherited. CT or sonographic demonstration of numerous medullary cysts in small kidneys and an appropriate clinical history should suggest this diagnosis. The end stage of the other entities in this category leads to small, hyperechoic kidneys at ultrasound (US) without in­­creased cyst formation.

Unilateral Smooth Renal Enlargement

In these cases, one kidney is abnormally large without focal mass effect. To determine which kidney is abnormal on standard radiographs, when there is a signifi­cant size discrepancy between the two kidneys, use the three-to-four-lumbar-vertebra rule. Normal-sized kidneys should have a length somewhere between the length of three and four normal lumbar vertebral bodies and their intervening disk spaces. On nonmagnifying cross-sectional imaging, a renal length of 10  to 12 cm is anticipated. In this category the contour of the enlarged kidney should be smooth or minimally lobulated in a manner consistent with persistent fetal lobation. In addition, there should be no evidence of focal renal masses affecting the renal collecting system. Renal function may be impaired; if so, this finding is helpful in classifying these cases. Underlying abnormalities resulting in this pattern fit into one of the following five categories: ureteral obstruction, renal duplication anomalies, acute vascular abnormalities, parenchymal infiltration, and glomerular hypertrophy ( Box 4-5 ).

The most common underlying abnormality in this group is ureteral obstruction. In the acute obstructive phase, the kidney is enlarged and edematous because of urinary outflow obstruction ( Fig. 4-11 ). Imaging after contrast material injection demonstrates the swollen kidney with delayed nephrographic progression and opacification of the collection system with a dense persistent nephrogram developing on later imaging ( Fig. 4-12 ). Varying degrees of hydronephrosis are evident depending on the severity and duration of obstruction. In many cases high-grade ureteral obstruction leads to a striated nephrogram . This term describes linear hypoattenuating regions (compared with a background of normally enhancing renal parenchyma) extending from the renal medulla into the renal cortex on a contrast-enhanced study of the kidney. This is most commonly seen with high-grade ureteral obstruction and is thought to be due to a combination of interstitial edema and stasis of unopacified urine in renal tubules adjacent to contrast-filled tubules ( Fig. 4-13 ).

As an aside, the striated nephrogram can be seen with a number of other entities, including autosomal recessive polycystic kidney disease, acute pyelonephritis, acute RVT, renal contusion, and immediately after radiation therapy to the kidney ( Box 4-6 ).