Renal parenchymal disease, also termed medical renal disease, includes various disorders of the glomeruli, interstitium, tubules, and small blood vessels of the kidneys. The clinical spectrum encompasses diseases confined to the kidneys and systemic disorders that secondarily affect the kidneys. Renal parenchymal diseases can be primary, secondary, congenital, hereditary, or acquired. There are various classification schemes. Categorization based on the predominantly affected parenchymal structures recognizes 3 major categories of medical renal disease: glomerular, tubulointerstitial, and vascular (Table 46-1). Many parenchymal diseases, however, substantially involve more than 1 of these anatomic divisions.

Sonography is the primary imaging technique for evaluation of most diseases of the renal parenchyma. Many renal disorders cause alterations in the echogenicity of the kidney parenchyma. Recognition of the normal changes in kidney echogenicity with age is essential for proper interpretation. The high concentration of glomeruli and prominent cellular volume of the neonatal renal cortex result in greater echogenicity than is typical for older children and adults. The echogenicity of the neonatal renal cortex is equal to or greater than that of the parenchyma of the liver and spleen. The medullary pyramids appear prominent and hypoechoic in the neonate, sometimes resembling dilated calyces to the unwary observer. The renal echogenicity assumes the adult pattern by about the age of 6 months, at which time the cortex is hypoechoic relative to the liver and spleen. The echogenicity of the medulla increases slightly during infancy, but remains hypoechoic to the cortex throughout life. Echogenic renal sinus fat tends to increase somewhat with age, and is scant or absent in the newborn.

Acute Renal Failure

The definition of acute renal failure is a sudden deterioration in renal function that results in inadequate excretion of nitrogenous wastes. Any insult that produces bilateral renal injury and failure of glomerular filtration can cause acute renal failure. Among these insults are ischemia, toxins, immunological disorders, and obstructive uropathy. In premature infants, dehydration, perinatal asphyxia, and congenital disorders are the most common causes. In older infants, severe dehydration and hemolytic uremic syndrome (HUS) are the most common precipitating events. In older children and adolescents, acute renal failure is most often due to acute glomerulonephritis (GN).^1–4

Acute renal failure can be categorized according to the character of the underlying condition. Prerenal azotemia indicates inadequate perfusion of the kidneys. Obstructive uropathy or postrenal azotemia refers to obstruction to the flow of urine. Intrinsic renal failure indicates a process that involves the renal parenchyma itself.

Prerenal azotemia is the most common cause of acute renal failure in the pediatric population as a whole. This can be caused by hemorrhagic shock, severe dehydration, cardiac insufficiency, or hypovolemia. Dehydration and other forms of prerenal azotemia are responsible for approximately 20% of cases of acute renal failure in children. If the underlying pathology is corrected promptly, return to normal renal function is likely.

Azotemia due to urinary tract obstruction requires the obstruction to be bilateral or to involve a solitary kidney. The most common cause of bilateral renal obstruction in children is posterior urethral valves. Other potential causes include pelvic or retroperitoneal neoplasm, trauma, and surgery. Prompt relief of the obstruction usually leads to resolution of the renal failure.

Processes that are associated with intrinsic renal failure in children can be categorized into those that predominantly involve the glomerulus (e.g., GN), the vascular supply of the kidney (e.g., renal artery thrombosis, renal vein thrombosis, HUS, disseminated intravascular coagulation, or vasculitis), or the tubules or interstitium of the kidney (e.g., acute tubular necrosis or acute interstitial nephritis). Intrinsic renal failure can occur in association with exposure of the kidney to various toxins. HUS is among the most common causes of acute renal failure in the pediatric population. Allergic interstitial nephritis accounts for up to 7% of instances of acute renal failure in children. Acute renal failure occurs as a complication in approximately 1% of children with idiopathic nephrotic syndrome.

For most children with acute renal failure, sonographic evaluation is important to document renal size, detect evidence of urinary tract obstruction, and assess renal perfusion. If hydroureteronephrosis is demonstrated, voiding cystourethrography may be a valuable adjunct. In those patients with prerenal azotemia or intrinsic renal failure, sonography usually shows increased parenchymal echogenicity, poor corticomedullary differentiation, and a variable degree of nephromegaly. Doppler studies may show increased resistive indices. Color Doppler is helpful for evaluating patency of the major renal arteries and veins. Although sonography is an essential component of the workup for the child with acute renal failure, the findings do not typically allow a specific diagnosis.^5,6

Chronic Renal Failure

A workgroup established under the auspices of the National Kidney Foundation has defined chronic kidney disease as the presence of clinically demonstrable kidney damage or a glomerular filtration rate (GFR) of less than 60 mL/min per 1.73 m² of at least 3 months duration. A GFR of 60 indicates a loss of approximately 50% of normal renal function; below this level, clinical manifestations of renal dysfunction become more common. Remaining nephrons may undergo progressive damage due to chronic hyperfiltration. Early detection of chronic kidney disease is essential to allow effective medical intervention and prevent or delay progression to renal failure.

The most useful measure of overall renal function is the GFR. This reflects the quantity of plasma ultrafiltrate that is presented to the renal tubular cells for processing and the formation of urine. The gold standard technique for GFR determination is the measurement of inulin clearance; inulin is filtered freely and is neither resorbed nor excreted. This is not used in standard clinical practice because it is invasive, time consuming, and costly. Estimation of GFR is commonly performed by measuring endogenous creatinine clearance or the clearance of filtration markers such as iothalamate, ⁵¹Cr-EDTA (ethylenediaminetetraacetic acid), gadolinium-DTPA (diethylenetriaminepentaacetic acid), or ^99mTc-DTPA.

Chronic renal failure in children may be congenital or acquired and primary or secondary. Congenital causes include obstructive uropathy, renal dysplasia, severe reflux nephropathy, juvenile nephronophthisis, polycystic kidney disease, cystinosis, oxalosis, and hereditary nephritis. Disorders that can produce the acquired form of chronic renal failure include GN, renal vascular disease, bilateral neoplasms (e.g., nephroblastomatosis, Wilms tumor), HUS, interstitial nephritis, and exposure to nephrotoxins.

The prevalence of chronic renal failure in the United States is 1.5 to 3 per million.⁷ The great majority of these patients are adults; pediatric patients account for only 1.4% of the total end-stage renal disease population.⁸ According to the North American Pediatric Renal Transplant Cooperative Study, the most common cause of chronic renal failure in children is obstructive uropathy (26%). Renal aplasia, hypoplasia, and dysplasia account for approximately 20%, reflux nephropathy 9%, and focal segmental glomerulosclerosis 6%.⁹

A variety of systemic and metabolic alterations can occur in children with chronic renal failure. Growth failure in these patients is predominantly due to disruption of the GH–IGF (growth hormone-insulin-like growth factor) axis.¹⁰ Delayed bone age is a common radiographic finding in patients with chronic renal failure.¹¹ Anemia (defined as hematocrit <30%) is present in 63% of pediatric patients with a GFR of less than 10 mL/min per 1.73 m², and in 13% of those with a GFR between 50 and 75 mL/min per 1.73 m².⁹ A high anion gap metabolic acidosis is a regular feature of chronic renal failure, particularly with a GFR in the range of 25 mL/min.¹² Approximately 70% of patients with chronic renal failure have hyperlipidemia.¹³ The prevalence of hypertension in children with renal disease is reported to be 38% to 78%.¹⁴ Secondary hyperparathyroidism is a common complication in patients with chronic renal failure, typically occurring early in the course of the disease.¹⁵

Intermittent imaging of the kidneys is indicated for most patients with chronic renal failure. Sonography is most useful, in part because it does not require the use of nephrotoxic contrast material. Substantial reduction in renal size suggests irreversible loss of renal function. Congenital renal cystic disease or findings of renal dysplasia are well demonstrated with sonography. Patients with sonographic evidence of hydronephrosis usually require further evaluation with additional imaging techniques.

Scintigraphy serves an important role for children with chronic renal failure to assess the amount of functioning renal tissue, quantify the GFR, and detect/characterize urinary tract obstruction. Voiding cystourethrography should be performed in children with suspected bladder outlet obstruction or vesicoureteral reflux.

Immune-Mediated Renal Diseases

Immune-mediated renal diseases can be classified according to the clinical syndromes they produce, by the associated renal pathology, or by the dominant immune effector mechanism of renal injury. The major clinical syndromes produced by immune-mediated renal injury include nephrotic syndrome, nephritic syndrome (acute GN), rapidly progressive GN, and acute renal failure. There is some clinical overlap between these syndromes.¹⁶

Hematuria

The definition of hematuria is grossly visible blood in the urine or the presence of red blood cells in the urine when viewed with a microscope. Up to 1% of clinically healthy infants have 5 or more red blood cells per high-power field on sequential urine specimens. Various classifications of hematuria are useful from a clinical standpoint. Hematuria can be isolated or painful. Terminal hematuria refers to that occurring in the later stages of voiding. Factitious hematuria can be produced by ingestion of various foods or medicines that produce a reddish discoloration of the urine without the presence of red blood cells. Various medical conditions can cause hematuria, including sickle cell disease, vasculitis, GN, strenuous exercise, coagulopathy, urolithiasis, occult trauma, and recent streptococcal infection. Hematuria accompanied by proteinuria suggests GN. The presence of white blood cells and organisms in the urine suggests that hematuria is due to a urinary tract infection. Hematuria sometimes occurs in a familial fashion. Rarely, severe or recurrent hematuria occurs due to a renal vascular malformation.

Sonography is the most appropriate imaging technique for the initial radiological evaluation of the child with isolated hematuria. Important potential findings include evidence of a structural abnormality of the urinary tract (e.g., hydronephrosis), urinary tract calculi, renal dysplasia, renal vein thrombosis, neoplasm, or renal infection. If the clinical and sonographic findings fail to establish a diagnosis, voiding cystourethrography is generally indicated. This is to evaluate for a bladder wall abnormality, vesicoureteral reflux, or urethral pathology (e.g., posterior urethral valves, Cowper duct cyst, urethral stenosis, or a lesion of the fossa navicularis).

If abdominal pain accompanies hematuria, the possibility of urolithiasis or ureteropelvic junction obstruction should be entertained. Ureteral obstruction in some patients with macroscopic hematuria is due to a blood clot (Figure 46-1). In young children with this history, the imaging workup usually consists of an abdominal radiograph and urinary tract sonography. If these studies are normal and there is a strong clinical suspicion of stone disease, helical CT of the abdomen and pelvis can be performed. In older children, helical CT is a reasonable selection as the initial imaging technique for patients with hematuria and pain. IV contrast should be utilized if there are any findings to suggest a tumor or parenchymal kidney abnormality.

In children who have suffered blunt abdominal trauma, the most commonly injured organs are the spleen, liver, and kidneys. Gross hematuria in a child with a history of abdominal trauma mandates a radiological evaluation, usually with contrast-enhanced CT. An emergency imaging investigation is not required, however, for isolated microscopic hematuria without any additional clinical or laboratory indicators of visceral trauma. In a patient with a pelvic fracture, gross hematuria or blood in the urethral meatus mandates evaluation of the urethra and bladder, usually with a retrograde and/or voiding cystourethrogram. Delayed and postdrainage pelvic films are essential for these patients to detect small contrast leaks from the bladder. Delayed CT imaging of the pelvis following IV contrast administration is a reasonable alternative to cystography for some patients with hematuria and pelvic trauma.

HUS is a microangiopathy that predominantly affects the kidneys; the intestine, lung, and brain can also be involved. This disorder is the major cause of acute renal failure in early childhood. The predominant characteristics of this disorder are acute renal insufficiency, microangiopathic hemolytic anemia, and thrombocytopenia. The primary pathogenic event in most patients with HUS is endothelial damage caused by a Shiga-like toxin (verotoxin) produced by a strain of Escherichia coli or by cytotoxic drugs (e.g., cyclosporin, mitomycin C). Glomerular endothelial cell injury or death results in a decreased GFR and accounts for many of the clinical manifestations of HUS. Release of vasoactive substances from damaged endothelial cells leads to a microangiopathic process that predominantly involves renal glomeruli and small renal arterioles. Coagulation abnormalities that can cause renal injury have also been identified, apparently due to accelerated thrombogenesis and inhibition of fibrinolysis; this can be a consequence of an E. coli 0157:H7 infection.¹⁷

The usual classification of HUS recognizes a diarrhea-associated “typical” form, D + HUS, and an atypical form without prodromal diarrhea, D – HUS. D – HUS comprises a heterogeneous group of diseases that includes genetic forms, such as autosomal recessive and dominant HUS, HUS secondary to complement dysregulation (e.g., factor H deficiency), and congenital and acquired von Willebrand factor protease deficiency. Untreated, the mortality rate of HUS approaches 90%. However, aggressive supportive care lowers the mortality rate to 5% to 10%, with most fatalities resulting from extrarenal complications.^18,19 End-stage renal disease following HUS occurs in 3% to 5% of patients, whereas chronic renal insufficiency and hypertension occur in approximately 15%.¹⁸ More than 80% of patients with D + HUS recover renal function; the mortality is approximately 5%. With D – HUS, only 60% to 70% of patients recover renal function. The case fatality rate is approximately 20%. Lack of evidence of Shiga-like toxin–producing E. coli infection also is associated with a poor prognosis.^20–22

As described above, HUS most often occurs in association with infection with Shiga-like toxin–producing E. coli (0157:H7) that causes a diarrheal illness.²³ The toxin binds to endothelial cell receptors and can cause cell death by the inhibition of cellular protein synthesis. Other organisms that occasionally cause HUS include Shigella dysenteriae type 1 and Streptococcus pneumoniae. HUS occurring in association with S. pneumoniae infection carries a greater risk for mortality and renal morbidity than does the more common E. coli–induced disease. The pathogenesis in these patients involves bacterial secretion of a neuraminidase that causes exposure of an antigen (T-antigen) on glomeruli, erythrocytes, and platelets, thereby allowing exposure of the antigen to circulating antibodies. The resultant antigen–antibody reaction (T-activation) causes anemia and the clinical manifestations of HUS.²⁴ There appear to be genetic factors that affect individual propensity for HUS, with both autosomal recessive and dominant patterns having been identified.²⁵

The clinical manifestations of HUS include nonimmune hemolytic anemia, thrombocytopenia, and renal disease. Most patients suffer a prodromal diarrheal illness, usually due to Shiga-like toxin–producing E. coli. Potential signs and symptoms of HUS include pallor, irritability, seizures (20%), heart failure, hypertension, GI bleeding, respiratory distress, and oliguria (Figure 46-2). Most patients are irritable and somnolent. There is considerable individual variation in disease severity; some patients have only a transient decrease in the volume of urine output. The acute renal failure usually lasts for 1 to 4 weeks, with subsequent slow improvement. Most often, there is complete clinical recovery, although some children have permanent neurological or renal damage. Occasionally, there is a progressive deterioration of renal function that progresses to chronic uremia. Extrarenal complications can occur within the GI tract, central nervous system, pancreas, and heart. Rarely, there is rapidly progressive myocardial dysfunction that can be fatal.²⁶

Imaging of HUS

During the acute phase of HUS, abdominal radiographs frequently demonstrate nephromegaly. The colon may be distended with gas; thumbprinting is sometimes visible, due to hemorrhage and edema in the colonic wall. The radiographic findings most often normalize with disease resolution; however, those children who sustain substantial kidney damage may develop manifestations of renal atrophy. Foci of cortical necrosis sometimes undergo calcification.

Sonographic examination is often useful for patients with HUS to determine kidney size and assess parenchymal abnormalities. Early in the disease, sonography is normal or shows nonspecific nephromegaly. Subsequently, the parenchyma develops abnormal increased echogenicity; this is typically most prominent in the glomerular and sub-cortical regions of the kidney (Figure 46-3). This increased echogenicity is predominantly due to calcifications and collagen deposition.²⁷

Doppler studies of children with HUS are helpful for assessing the severity of illness and predicting the time course to recovery. The intrarenal vasculitis results in elevated vascular impedance and diminished peripheral renal arterial flow during diastole. With severe involvement, intrarenal arterial flow may not be detectable, or diastolic flow may be absent or reversed. As the disease improves, return of appropriate early diastolic flow is the first finding. Return of the Doppler signal pattern to normal occurs when the arteriolar obstruction resolves.

Measurement of the resistive index is an important part of the Doppler evaluation of HUS and many other disorders that affect the renal parenchyma or peripheral renal vessels. The resistive index is defined as the peak systolic flow velocity minus the diastolic flow velocity divided by the diastolic flow velocity. The resistive index is, for the most part, a reflection of resistance to blood flow into the organ of interest; the closer the resistive index is to 1, the higher the resistance to flow. A value of 1 indicates stagnant or reversed diastolic flow. In addition to vascular resistance, factors that influence the resistive index include vessel compliance, the cross-sectional area of the downstream vascular bed, hydration status, and heart rate. The renal artery resistive index varies somewhat with age. The normal renal artery resistive index can measure up to 0.9 in preterm infants, between 0.6 and 0.8 in infants and term neonates, and 0.5 to 0.7 in older children. In children with HUS, the greatest alteration in the resistive index occurs during the oliguric or anuric phase of the disease. Normalization of the arterial waveforms usually occurs 1 to 2 days prior to recovery of renal function.^28–30

GN refers to various disorders in which there is disruption of the normal glomerular filtration mechanism, usually due to inflammation of the glomerular capillaries. Enlarged pores in the podocytes of the glomeruli allow passage of proteins and red blood cells into the urine. Primary renal diseases that present with acute GN include poststreptococcal GN, Immunoglobulin A (IgA) nephropathy, membranoproliferative GN, and idiopathic rapidly progressive GN (rare in children). Acute GN can also occur in association with a variety of systemic disorders.

The classic clinical pattern of acute GN is the acute onset of hematuria, proteinuria, and hypertension in a previously well child. Oliguria, edema, and cardiovascular manifestations of fluid overload may also be present. The presenting symptom is usually the sudden onset of gross hematuria. Renal function may be normal or impaired. This constellation of signs and symptoms is the acute nephritic syndrome.

Hypertension occurs in 60% to 80% of patients with acute GN. The blood pressure elevation is usually mild to moderate in severity. The mechanism of hypertension in these patients apparently involves intracellular volume expansion and generalized vasospasm. Most often, there is spontaneous resolution of hypertension, beginning within a few weeks of the onset.

Poststreptococcal acute GN is now infrequent in developed countries, where it occurs only sporadically. This is, however, still a major health problem in some parts of the world. The propagation of the responsible organism within the community is interrupted by timely diagnosis and treatment. The condition is associated with infections with some types of group A β-hemolytic streptococci. Immune complexes are formed with streptococcal antigens. These localize on the glomerular capillary wall and initiate a proliferative and inflammatory response. The potential clinical manifestations include soft tissue edema, arterial hypertension, oliguria, hematuria, and proteinuria. There is usually mild-to-moderate elevation of serum creatinine. C3 is decreased. Most patients recover without permanent sequelae. Potential complications include congestive heart failure, hypertensive encephalopathy, and acute renal failure.³¹

IgA nephropathy (Berger nephropathy) is an acute GN in which IgA is the predominant immunoglobulin in mesangial deposits. By definition, these patients have no evidence of an associated systemic disease such as Henoch-Schönlein purpura (HSP). Young adults and older children are most often affected. There is a 2:1 male predominance. Nearly all patients with IgA nephropathy have gross or microscopic hematuria.

The diagnostic imaging findings of acute GN are variable. Bilateral nephromegaly is common. On CT and IV urography, parenchymal enhancement is homogeneous, but is sometimes reduced in intensity. There is often abnormally increased cortical echogenicity on sonography, with or without deficient corticomedullary differentiation. Potential findings on chest radiographs include cardiomegaly, pulmonary vascular congestion, septal edema, and chest wall edema (Figure 46-4). Pleural effusions are usually small. Airspace opacification due to pulmonary edema occurs in approximately 25% of patients. Nephrotic syndrome differs in that the pleural effusions are larger, the lungs are clear, and heart size is normal.

Chronic GN is uncommon in children. Tissue damage and progression to interstitial fibrosis in chronic GN result from an immune response that causes excessive inflammation. There is glomerular influx of activated inflammatory cells that release autocoids and destructive enzymes. Glomerular cells become activated as well and undergo proliferation and subsequent apoptosis, thereby contributing to inflammation and fibrosis. The initial trigger for these events involves immune complexes that are either deposited from the circulation or formed in situ. In the absence of glomerular immune deposits, the condition is termed “pauci-immune GN.” Hypertension often occurs in patients with severe forms of chronic GN and secondary renal failure.

Renal imaging of patients with chronic GN demonstrates normal-sized or bilaterally small kidneys with smooth borders. The typical sonographic appearance is prominent cortical echogenicity, with preserved corticomedullary differentiation. Doppler evaluation frequently demonstrates diminished renal blood flow, but normal resistive index measurements.^16,32