Congenital urinary tract obstruction occurs most frequently in males, most commonly as a result of either posterior urethral valves or pelviureteral junction (PUJ) obstruction. If obstruction occurs early during development, the kidney fails to develop and becomes dysplastic. If the obstruction is bilateral, there is a high mortality rate as a result of severe renal failure. If the obstruction occurs later in gestation and is low grade or unilateral, hydronephrosis and nephron loss will still occur, but renal function may be sufficient to allow survival, and such patients may not present until later in childhood. Pelviureteral junction obstruction, if it is mild, may not present until adulthood and in some patients may be an incidental finding (Fig. 60-1). However, with increased use and improved sensitivity of antenatal scanning, congenital abnormalities of the urinary tract are now frequently identified early, allowing prompt postnatal (and in some cases antenatal) intervention to relieve the obstruction and hence to preserve renal function. Congenital causes of obstruction are discussed further in Chapter 52.

Changes in Glomerular Function

Glomerular filtration rate (GFR) declines progressively after the onset of complete ureteral obstruction.⁴ Glomerular filtration is determined by the mean hydraulic pressure gradient between the glomerular capillary lumen and Bowman space, the renal plasma flow, the ultrafiltration coefficient of the glomerular capillary wall, and the mean oncotic pressure difference across the glomerular wall. Obstruction can affect all of these, and the effects vary with the duration of the obstruction, the hydration state, and presence or absence of a contralateral functioning kidney.

After complete ureteral obstruction, there is an initial rise in proximal tubular pressure. At the same time, afferent arteriolar dilation occurs as a result of the generation of vasodilatory prostaglandins. Glomerular capillary hydraulic pressure increases, but this does not offset the rise in tubular pressure, and there is a net decrease in the hydraulic pressure gradient across glomerular capillaries, resulting in an 80% decline in GFR.⁴

About 2 to 5 hours after obstruction, renal blood flow begins to decline, whereas intratubular pressure continues to increase. Within 5 hours, proximal tubular pressure begins to decline toward control values. From this time, the main determinant of the decrease in GFR is the fall in intraglomerular capillary pressure as a result of an increase in resistance of afferent arterioles. This results in a progressive fall in renal plasma flow, which reaches 30% to 50% of control values by 24 hours. Preferential constriction of the preglomerular blood vessels lowers both plasma flow and glomerular capillary pressure, resulting in a greater decrement in GFR than in plasma flow and a fall in filtration fraction. A falling filtration fraction also results from diversion of blood to nonfiltering areas of the kidney or a reduction in the ultrafiltration coefficient.⁴ The relative changes in ureteral pressure, renal plasma flow, and GFR are summarized in Figure 60-3.

The intrarenal vasoconstriction results from the generation of angiotensin II and thromboxane A₂, the release of vasopressin (antidiuretic hormone), and decreased nitric oxide production. Intrarenal angiotensin II generation occurs secondary to an increase in renin release either through reduced delivery of sodium and chloride to the distal nephron (macula densa mechanism) or through a reduction in transmural pressure at the baroreceptor as a consequence of the prostaglandin-dependent dilation of the afferent arteriole. Generation of thromboxane A₂ occurs in both glomeruli and infiltrating interstitial cells. Angiotensin II and thromboxane A₂ may also reduce the ultrafiltration coefficient. The central role of these two vasoconstrictors has been demonstrated by studies in rats, in which pretreatment with angiotensin-converting enzyme inhibitors and thromboxane synthase inhibitors virtually normalized renal function after the relief of short-term ureteral obstruction.⁵

An interstitial leukocyte infiltrate, predominantly macrophages, develops in response to chemoattractants such as monocyte chemoattractant protein 1 and osteopontin expressed by tubular cells. This infiltrate plays a key role in the acute functional changes after ureteral obstruction⁶ and the pathogenesis of the late structural changes that occur after obstruction as macrophage depletion limits experimental interstitial fibrosis.⁷

The extent to which glomerular function recovers after the release of ureteral obstruction depends on the duration of the obstruction. Whole kidney GFR may return to normal after short-term obstruction (days), whereas recovery may be incomplete after prolonged obstruction. Evidence from studies in rats suggests that even with shorter periods of obstruction (72 hours), there may be a permanent loss of nephrons, and whole kidney GFR returns to normal only at the expense of hyperfiltration (increase in single nephron GFR) in the remaining functional nephrons.⁸

Changes in Tubular Function

Abnormalities in tubular function are common in urinary tract obstruction and manifest as altered renal handling of electrolytes and changes in the regulation of water excretion.⁹ The degree and nature of the tubular defects after obstruction depend in part on whether the obstruction is bilateral or unilateral. These differences could result from the dissimilar hemodynamic responses, different intrinsic changes within the nephron, differences in extrinsic factors (e.g., volume expansion and accumulation of natriuretic substances in bilateral obstruction) between the two states, or a combination of all three.

After ureteral obstruction, the ability to concentrate the urine is markedly impaired, with maximum values of 350 to 400 mOsm/kg reported in the rat. Causative factors include a loss of medullary tonicity, an overall decrease in GFR in deep nephrons, and a reduced expression of sodium transporters.¹⁰ Also, the collecting duct is unresponsive to vasopressin because of a reduction in the expression of renal aquaporins that results from both cyclooxygenase-2 activity¹¹ and angiotensin II.¹²

Rats exhibit reduced expression of multiple acid-base transporters after ureteral obstruction,¹³ and patients with urinary tract obstruction often exhibit urinary acidification defects. These defects may be detected only by exogenous acid loading, but hyperchloremic acidosis caused by impaired distal acid secretion, hyporeninemic hypoaldosteronism (type IV renal tubular acidosis), and a combination of these findings have been described. This acidifying defect results from a marked increase in bicarbonate excretion or from a distal acidification defect, possibly as a result of abnormalities of the H⁺-ATPase activity of intercalated cells of the collecting duct after ureteral obstruction.

Obstruction alters renal potassium handling. In the presence of a normal functioning contralateral kidney, potassium excretion is reduced after relief of obstruction, either in proportion to or perhaps even exceeding the fall in GFR (i.e., fractional excretion of potassium is unaltered or slightly reduced). There is a defect in the distal potassium secretory mechanism after unilateral obstruction that may be secondary to reduced responsiveness of that nephron segment to aldosterone. By contrast, after release of bilateral ureteral obstruction, there is a marked increase in both net and fractional potassium excretion. The major mechanism by which potassium losses occur in this setting is an increased delivery of sodium to the distal tubule, resulting in an accelerated sodium-potassium exchange.

Recovery of tubular function after release of obstruction is slow and may remain abnormal even after whole-kidney GFR has returned to normal. In rats, acidification and potassium-handling abnormalities persist for at least 14 days and urinary concentrating ability is abnormal for up to 60 days after the release of 24 hours of unilateral ureteral obstruction. These observations are consistent with persistent alterations in distal tubular and collecting duct function or a loss in functioning juxtaglomerular nephrons after the release of the obstruction.

Histopathologic Changes

The morphologic alterations in renal architecture are similar irrespective of the cause of the obstruction. Initially, renal enlargement and edema occur with pelvicalyceal dilation (Fig. 60-4). Tubular dilation that predominantly affects the collecting duct and distal tubular segments develops microscopically, although cellular flattening and atrophy of proximal tubular cells can also occur. Glomerular structures are usually preserved initially, although Bowman space may be dilated and some periglomerular fibrosis may ultimately develop.