The principal functions of the kidneys are the maintenance of water, electrolyte, and acid-base balance, elimination of waste products, and regulation of blood pressure. The functional unit of the kidney is a nephron, which consists of a glomerulus and a tubule, and urine is formed as a result of glomerular filtration, tubular reabsorption, and tubular secretion [1].

The glomerulus consists of a network of capillaries derived from the afferent glomerular arteriole. The glomerular capillary tuft acts as a filter for plasma. It is encased by two epithelial layers, the inner layer becoming part of the outer capillary wall and the outer layer lining Bowman’s space (capsule), which receives the filtered fluid. The glomerular filtration rate (GFR) is dependent largely on the hydrostatic and colloid osmotic pressure in the glomerular capillaries and the hydrostatic pressure in Bowman’s space. Filtered fluid from Bowman’s space enters the tubule, which can be broadly divided into several portions: the proximal tubule, loop of Henle, distal tubule, collecting tubule, and collecting duct system (Fig. 10.1).

The proximal tubule plays a key role in reabsorbing filtered solutes. About half to two thirds of the sodium, chloride, and potassium are reabsorbed in this segment. Reabsorption of solutes is accompanied by passive osmotic diffusion of water.

The loop of Henle, consisting of a descending limb and an ascending limb, is the site of reabsorption of about 25 % of the filtered solutes. Reabsorption occurs primarily in the “thick” ascending limb, where the epithelial cells are thick and metabolically very active. It is in this section that “loop” diuretics such as furosemide exert their effects (see later). The reabsorbed solutes enter the medullary interstitium and contribute to its hypertonicity.

The distal tubule transports sodium, chloride, and potassium, but not water, from its proximal part, similar to the loop of Henle. The terminal distal tubule shares similar functions with the collecting tubules (see later). At the very beginning of the distal tubule is the macula densa, a region of specialized cells in close proximity to the juxtaglomerular (JG) cells in the afferent arteriole that store renin. In response to changes in sodium and chloride concentration in this portion of the tubule, the macula densa sends signals to the JG cells to release renin.

The collecting tubule and terminal distal tubule are under the influence of aldosterone and antidiuretic hormone (ADH). Aldosterone, released from the zona glomerulosa of the adrenal cortex in response to angiotensin II, increases potassium secretion and sodium reabsorption. The latter promotes water reabsorption by osmosis and raises blood volume. ADH, originating in the hypothalamus and posterior pituitary and released in response to a rise in osmotic pressure of extracellular fluids or low blood pressure, increases the permeability of the cortical collecting ducts to water, which helps to maintain body fluid osmolality and effective plasma volume and to form concentrated urine. A hyperosmotic medullary interstitium, primarily the result of reabsorption of solutes from the thick ascending limb of the loop of Henle, also contributes to the reabsorption of fluid and the formation of concentrated urine.

Furosemide, used for the scintigraphic evaluation of urinary tract obstruction, and other loop diuretics block the reabsorption of sodium, chloride, and potassium in the thick ascending limb of the loop of Henle. Increased tubular sodium decreases water reabsorption by an osmotic effect. Additionally, decreased sodium reabsorption into the medullary interstitium reduces its osmolarity, which in turn reduces water reabsorption from the collecting tubules.

The renal artery enters through the hilum of the kidney and branches successively into the interlobar arteries, arcuate arteries, interlobular arteries, and afferent arterioles. Each afferent arteriole eventually branches into the glomerular capillaries. The distal glomerular capillaries merge to form the efferent arteriole. Efferent arterioles subdivide to form peritubular capillaries in the cortex or the vasa recta in the medulla. As discussed later, changes in the afferent or efferent arteriolar tone play an important role in regulating the GFR.

The afferent arteriole has specialized smooth muscle cells called juxtaglomerular (JG) cells that store renin and stretch receptors that respond to changes in arteriolar pressure. Renin is released as a result of decreased stretch of the arteriolar wall when arteriolar pressure is decreased. Another stimulus for renin comes from the macula densa, which consists of specialized cells in the first part of the distal tubule, and is located close to the JG cells. The macula densa signals the JG cells to release renin when the sodium and chloride content of this part of the tubule is low. Finally, the sympathetic nervous system can stimulate renin release in response to systemic baroreceptor stimuli. These mechanisms are discussed further under Sect. 10.4.

Based on kinetics, renal radiopharmaceuticals can be divided into two broad classes—those that are excreted rapidly into the urine and those that are retained for prolonged periods in the renal parenchyma. In the first category are ^99mTc-mercaptoacetyltriglycine (MAG3), ^99mTc-diethylenetriamine pentaacetic acid (DTPA), and ¹³¹I-orthoiodohippurate (OIH) and, in the second category, ^99mTc-dimercaptosuccinic acid (DMSA) and ^99mTc-glucoheptonate.

The teleological function of the renin-angiotensin system, i.e., maintenance of systemic blood pressure, is well served in such conditions as hypotension and shock. In significant renal artery stenosis, however, activation of the renin-angiotensin system is a mixed blessing, limiting a fall in GFR but causing systemic (renovascular) hypertension. Systemic blood pressure is maintained primarily by increase in vascular tone and retention of sodium and water, while a sharp reduction in GFR is prevented by increase in the glomerular capillary hydrostatic pressure.

Glomerular capillary hydrostatic pressure is modulated by the tone of the afferent and efferent glomerular arterioles. Increased tone in the efferent arteriole or decreased tone (increased flow) in the afferent arteriole raises capillary hydrostatic pressure and GFR, while decreased tone in the efferent arteriole or increased tone (decreased flow) in the afferent arteriole lowers GFR.

The first step in the activation of the renin-angiotensin system is the release of renin by the renal JG cells. The following mechanisms are involved [8, 9]:

Renin released as a result of the above stimuli converts circulating angiotensinogen, an alpha₂ globulin produced by the liver, to angiotensin I, a decapeptide. Angiotensin I is then converted to the active octapeptide form, angiotensin II, by angiotensin-converting enzyme (ACE), found in vascular endothelium, and the bulk of this conversion occurs in the pulmonary vascular bed. Angiotensin II is also produced in the kidney.

Urinary tract obstruction may be complete or partial, and it may occur at various locations including the ureteropelvic junction (UPJ), ureterovesical junction (UVJ), and bladder outlet. The clinical consequences are quite dramatic and predictable in an acute and complete obstruction, but not in a partial and chronic one, exemplified by UPJ obstruction in children. Chronic UPJ obstruction, however, may eventually lead to renal cortical atrophy. Hence diagnostic markers are needed to identify those patients at risk of progressive renal insufficiency.

Despite a large body of literature on the diagnostic evaluation of urinary tract obstruction, the identification of “significant obstruction,” i.e., one that would result in progressive renal failure, remains somewhat elusive. This is because significant obstruction is probably much more a functional entity than an anatomical one, and left untreated, similar types of obstruction may have markedly dissimilar outcomes. This section is devoted primarily to chronic (partial) UPJ obstruction in infants and young children, an entity frequently encountered by the nuclear medicine physician, and its relationship to hydronephrosis and renal function.

UPJ obstruction may be extrinsic or intrinsic, and both conditions may exist in the same patient. Extrinsic obstruction is usually caused by adventitial bands compressing the upper ureter. Typically, this type of obstruction is intermittent and brought on by increased diuresis, which dilates the pelvis and increases the constrictive pressure of the adventitial bands. As might be expected, pressure-flow studies of the renal pelvis are not linear in this condition. More importantly, the diuretic renogram may be negative if adequate diuresis, i.e., adequate dilatation of the pelvis, is not achieved because of dehydration, inadequate diuretic dosage, or renal dysfunction.

Intrinsic obstruction may be related to luminal narrowing of a segment of the upper ureter or to an adynamic segment. This type of obstruction generally exhibits a linear pressure-flow relationship, and although considered “fixed,” the obstruction is not necessarily permanent and does not invariably cause progressive renal deterioration.

Hydronephrosis may be due to obstruction or to such nonobstructive conditions as vesicoureteral reflux, congenital dysmorphism, and urinary tract infection. It may be temporary with spontaneous resolution in infants and young children, or intermittent, or progressive with eventual stabilization. Such variability is related to the multifactorial etiology of hydronephrosis [34–36]. These factors include the following:

Progression or stabilization of hydronephrosis depends on the degree of balance between these factors. Pressure in the renal pelvis, though not measurable by diuretic renography, is a critical component in the pathogenesis of hydronephrosis and renal dysfunction. Pressure-flow studies suggest that the pelvis fills at low pressures initially until a critical volume (“capacity”) is reached, above which the pelvic pressure rises. Subsequent development of hydronephrosis tends to relieve pelvic pressure. A low-capacity pelvis is more likely to have higher pelvic pressures with progressive hydronephrosis. In this instance, cortical atrophy eventually occurs, with decrease in urine formation and reduction of pelvic pressure.

Diuretic renography [35–39] is based on the premise that increased urine flow resulting after furosemide administration causes rapid “washout” of radiotracer from the unobstructed collecting system (Fig. 10.2), but delayed washout if obstruction is present (Fig. 10.3). While furosemide generally is administered intravenously after filling of the pelvicalyceal system, administration at the time of or prior to radiotracer administration also has been advocated. The washout half-time following diuretic injection is determined from the time-activity curve. A half-time of 10 min or less is considered normal, 10–20 min equivocal, and more than 20 min abnormal. However, over-reliance on the washout half-time may not be justified because a number of factors may influence the diuretic renogram.