Obstructive Nephropathy: Pathophysiology and Management

Obstructive Nephropathy: Pathophysiology and Management

Kevin P. G. Harris


Urine that is produced by the kidney is conveyed to the urinary bladder by the renal pelvis and ureter. This relies on peristalsis occurring within the ureters and, during high urine flow rates, the pressure gradient along them. The urinary bladder is a muscular and distensible storage compartment with a capacity of up to 800 mL in humans. At about a capacity of 150 to 400 mL, stretch receptors result in neurologic signals which relax the involuntary internal urethral sphincter and result in the sensation of needing to urinate, although urination may be delayed by conscious control of the external urethral sphincter as long as the capacity of the bladder is not exceeded. Conscious relaxation of the external urethral sphincter allows urine to be voided through the urethra.

The normal elimination of urine from the body may be affected by pathology anywhere along the urinary tract which either results in a physical barrier to urine flow or disrupts the complex neurologic processes which control it. This is referred to as obstructive uropathy. Typically dilatation of the urinary tract or hydronephrosis then occurs proximal to the site of obstruction, a change which can be readily detected with a variety of imaging techniques. However, hydronephrosis is not synonymous with obstructive uropathy as it can occur without functional obstruction to the urinary tract and can be absent in established obstruction, for example in vesicoureteral reflux (VUR), primary megaureter, and diabetes insipidus.

Impedance to the flow of urine initially results in a high back pressure which causes a number of direct and indirect functional effects on the renal parenchyma, referred to as obstructive nephropathy.

Immediately following acute urinary tract obstruction, changes within the kidney are mainly functional resulting in acute kidney injury (AKI) which may recover with prompt and effective relief of the obstruction. If left untreated, obstruction will result in irreversible structural damage and scarring within the kidney leading to chronic kidney disease (CKD). The management of obstruction to the urinary tract requires close collaboration between nephrologists and urologists in order to minimize long-term and irreversible damage to the kidney, but despite this urinary tract obstruction remains a major cause of CKD worldwide.

Obstructive uropathy is classified as to whether it is acute (less than a few days duration) or chronic and whether it is complete (high grade) or incomplete and partial (low grade). Obstruction is further subdivided into whether it affects the upper urinary tract obstruction (usually unilateral obstruction occurring above the vesicoureteral junction [VUJ]) or lower urinary tract obstruction (usually bilateral obstruction located below the VUJ). Classifying obstruction in this way predicts the likely pathophysiologic effects on the patient; for example, unilateral obstruction in a patient with two normal kidneys will not result in significant renal impairment because the contralateral kidney compensates, but bilateral obstruction or the obstruction of a single functioning kidney will result in renal failure.

Obstruction may result from either acquired or congenital abnormalities. Acquired urinary tract obstruction may affect either the upper or lower urinary tract and can result from either intrinsic or extrinsic causes. Intrinsic causes of obstruction may be intraluminal or intramural.

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 preserve renal function (1). 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. Such patients may not present until later in life or only be discovered as an incidental finding.

Incidence and Prevalence

Obstructive uropathy is a common entity and can occur at all ages. The exact incidence of obstructive uropathy is difficult to ascertain, since obstruction occurs in a variety of diseases that may warrant hospitalization and surgical intervention and may be transient. However, the prevalence of hydronephrosis at autopsy is 3.5% to 3.8% of adults and 2% of children, with about equal distribution between males and females (2).

The frequency and etiology of obstruction vary in both sexes with age. Congenital urinary tract obstruction occurs most frequently in males, commonly as a result of either posterior urethral valves or pelvic-ureteral junction (PUJ) obstruction explaining the higher rate of obstructive uropathy in male children less than 10 years old.

In the United States, congenital obstructive uropathy remains the single most common cause of end-stage renal disease (ESRD) in pediatric patients (0-21 years) accounting for about 9% of incident patients (3) and despite improvements in the treatment, this condition may continue to impact into adult life.

Beyond 20 years of age, obstruction becomes more common in females, mainly as a result of pregnancy and gynecologic malignancies. Urolithiasis occurs predominantly in young adults (25-45 years old) and is three times more common in men than in women. In patients older than 60 years, obstructive uropathy is seen more frequently in men, secondary to benign prostatic hyperplasia and prostatic carcinoma. About 80% of men older than 60 years have some symptoms of bladder outflow obstruction, and up to 10% have hydronephrosis. Although the exact relationship between symptoms of bladder outflow obstruction and CKD is unclear, there appears to be a significant association between a decreased peak flow rate and CKD (4).

In the United States the incidence of ESRD due to acquired obstruction is 0.9% with 76% being male and 61% being over the age of 65 (3). However, this is dwarfed by comparison with other causes of ESRD in the adult population such as glomerular disease, diabetes, and hypertension.

Causes of Obstructive Uropathy

The major causes of obstructive uropathy are described in Table 12-1.

Intrarenal tubular obstruction can result from the deposition of uric acid crystals in the tubular lumen after treatment of hematologic malignancies (tumor lysis syndrome), with the precipitation of Bence Jones protein in myeloma and with the precipitation or crystal formation of a number of drugs, including sulfonamides, acyclovir, methotrexate, and indinavir.

Renal calculi, which typically lodge in the calyx, PUJ, or VUJ and at the level of the pelvic brim are the most common cause of extrarenal intraluminal obstruction. Calcium oxalate stones (the most common form) typically cause intermittent acute unilateral urinary tract obstruction in young adults, but rarely significant renal impairment. Struvite, urate, and cystine stones are more often bilateral and more likely to cause long-term renal impairment. Papillary necrosis and a sloughed papilla from diabetes mellitus, sickle cell trait or disease, analgesic nephropathy, renal amyloidosis, and acute pyelonephritis may result in intraluminal obstruction as may blood clots following macroscopic hematuria as a result of renal tumors, arteriovenous malformations, renal trauma, or in patients with polycystic kidney disease (clot colic).

Intramural obstruction can result from either functional or anatomic changes. Functional disorders include VUR, adynamic ureteral segments (usually at the junction of the ureter with the pelvis or bladder), and neurologic disorders. The latter may result in a contracted (hypertonic) bladder or a flaccid (atonic) bladder, depending on whether the lesion affects upper or lower motor neurons, and lead to impaired bladder
emptying with VUR. Bladder dysfunction is very common in patients with multiple sclerosis and after spinal cord injury, and is also seen in diabetes mellitus and Parkinson disease and after cerebrovascular accidents. Some drugs (anticholinergics, levodopa) can alter neuromuscular activity of the bladder and result in functional obstruction, especially if there is preexisting bladder outflow obstruction (e.g., prostatic hypertrophy). Anatomic causes of intramural obstruction of the upper urinary tract include transitional cell carcinoma of the renal pelvis and ureter and ureteral strictures secondary to radiotherapy or retroperitoneal surgery. Rarely, obstruction may result from ureteral valve malfunction, polyps, or strictures after therapy for tuberculosis. Intramural obstruction of the lower urinary tract can result from urethral strictures, which are usually secondary to chronic instrumentation or previous urethritis, or malignant and benign tumors of the bladder. Infection with Schistosoma haematobium, when the ova lodge in the distal ureter and bladder, is a common cause of obstructive uropathy worldwide, with up to 50% of chronically infected patients developing ureteral strictures and fibrosis with contraction of the bladder.

Table 12-1 Causes of Obstruction in the Urinary Tract

Upper Urinary Tract

Lower Urinary Tract

Intrinsic Causes


  • Intratubular deposition of crystals (uric acid, drugs) or Bence Jones protein

  • Ureter: stones, clots, renal papillae, fungus ball


  • Ureteropelvic or ureterovesical junction dysfunction

  • Ureteral valve, polyp, stricture, or tumor

Anatomic Causes

  • Phimosis, meatal stenosis, paraphimosis

  • Urethra: strictures, stones, diverticulum, posterior anterior urethral valves, urethral infections, periurethral abscess, uretheral surgery

  • Prostate: benign prostatic hyperplasia, abscess, prostatic carcinoma

  • Bladder: calculus, malignancy

  • Trauma, straddle injury

  • Pelvic fracture

Extrinsic Causes

Originating in the reproductive system

  • Uterus: pregnancy, prolapse, tumors, endometriosis

  • Ovary: abscess, tumors,

  • Cervix: carcinoma

  • Prostate: carcinoma

Vascular system

  • Aneurysm: abdominal aorta, iliac vessels

  • Aberrant vessels: ureteropelvic junction

  • Venous: retrocaval ureter, ovarian vein

  • Fibrosis following vascular reconstructive surgery

Lesions of the gastrointestinal tract

  • Crohn disease

  • Diverticulitis

  • Appendiceal abscess

  • Tumors, abscess, cyst

Diseases of the retroperitoneum

  • Retroperitoneal fibrosis (idiopathic radiation)

  • Inflammatory: tuberculosis, sarcoidosis

  • Hematomas

  • Primary retroperitoneal tumors (lymphoma, sarcoid)

  • Metastatic disease in the retroperitoneum (cervix, bladder, colon, prostate)

  • Lymphocele

Inadvertent surgical ureteric ligation

Functional Causes

  • Neurogenic bladder: spinal cord defect or trauma, diabetes, multiple sclerosis, cerbrovascular accidents, Parkinson disease

  • Drugs: anticholinergics, antidepressants, L-DOPA

While ureteral dilation without functional obstruction is commonly seen in pregnancy as a result of hormonal effects (especially progesterone) on smooth muscle, extrinsic obstruction sometimes resulting from compression of the urinary tract is pressure from a gravid uterus on the pelvic rim with the right ureter being more commonly affected. It is usually asymptomatic, the changes resolve rapidly after delivery, and AKI from bilateral obstruction is very rare.

Extrinsic obstruction may result from malignancy compressing or directly invading the urinary tract. Direct extension of the tumor to involve the urinary tract occurs in up to 30% of patients with carcinoma of the cervix. Other pelvic pathologies that can cause ureteral compression include benign and malignant uterine and ovarian masses, abscesses, endometriosis, and pelvic inflammatory disease.

In males, the most common cause of extrinsic obstruction of the lower urinary tract is benign prostatic hypertrophy. Carcinoma of the prostate can also result in obstruction either from direct tumor extension to the bladder outlet or ureters or from metastases to the ureter or lymph nodes.

Retroperitoneal pathology such as primary or secondary tumors or inflammatory disease may also result in extrinsic obstruction of the ureters. Retroperitoneal fibrosis, in which a thick fibrous tissue extends out from the aorta to encase the ureters and draw them medially, may be idiopathic or result from inflammatory aortic aneurysms, certain drugs (e.g., β-blockers, bromocriptine, and methysergide), previous radiation, trauma or surgery, and granulomatous disease.

Inadvertent ureteric ligation is a rare but recognized complication of pelvic surgical procedures and may go unrecognized.

The Effects of Urinary Tract Obstruction on Renal Function

The increased pressure that occurs after the onset of ureteral obstruction triggers profound functional and structural changes within the kidney. This increase in pressure is greatest immediately after the onset of obstruction and tends to fall with time with incomplete obstruction. Damage in the obstructed kidney is potentiated by those conditions that acutely increase ureteral pressure, such as increases in urine flow (i.e., an increase in fluid intake or after administration of diuretics) or augmentation of the degree of obstruction or both.

It is rarely possible to accurately define the time of onset of obstruction in humans or to obtain repetitive measurements of renal function. Therefore, our understanding of the consequences of urinary tract obstruction stems mainly from the study of animal models (5). The majority of studies have used invasive techniques to examine the effects of complete short-term ureteral obstruction in rodents. Investigators have also examined models of chronic complete, partial, or reversible obstruction in adult and neonatal animals and modern imaging techniques have been used to noninvasively examine the effects of obstruction on glomerular and tubular function (6). In general, there appears to be little species-to-species variation in the response to acute obstruction, suggesting similar changes are likely to occur in humans. Although initially the changes are predominantly functional and potentially reversible, chronic obstruction results in irreversible structural changes (7), and models of obstruction are often used to examine the pathogenetic mechanisms underlying the development of renal fibrosis from any cause (8).


Experimental evidence suggests that ureteral obstruction may reduce glomerular filtration rate (GFR) though effects on (a) the mean difference in hydrostatic pressure between the glomerular capillary lumen and Bowman’s space (ΔP); (b) renal plasma flow (QA); (c) the ultrafiltration coefficient of the glomerular capillary wall (Kf), which reflects both the total surface area available for filtration and the intrinsic permeability characteristics of the filtering apparatus. The manner in which these parameters are affected depends on the duration of the obstruction, the volume status of the animal, and whether or not a contralateral functioning kidney is present.

GFR falls progressively following the onset of complete ureteral obstruction (9) but can be maintained to some extent by continuous reabsorption of salt and water along the nephron, the ability of the renal tract to dilate, and alterations in renal hemodynamics.

Changes in Hydrostatic Pressure Gradients

Ligation of the ureter increases ureteral pressure causing an immediate increase in proximal tubular pressure, the latter being higher than that in the ureter. The rise in intratubular pressure depends on the degree of hydration of the animal, mean urine flow rate, and whether one or both kidneys are obstructed. Nevertheless, independent of the volume status, intratubular pressure rises within an hour of ureteral obstruction (Fig. 12-1). Concomitantly, there is an increase in glomerular capillary hydrostatic pressure; however, this increase in
intraglomerular pressure is not proportional to the rise in intratubular pressure (10). Therefore, the net hydrostatic pressure difference across glomerular capillaries decreases. This results in a decline in GFR. After approximately 5 to 6 hours of ureteral obstruction, proximal intratubular pressure begins to decline (11). After 24 hours, intratubular pressures are lower than (11, 12) or equal to (13) values before obstruction in animals with unilateral ureteral obstruction (UUO), but this does not restore an effective filtration pressure, because intraglomerular capillary hydrostatic pressure declines at an even faster rate (11, 12) and falls below the levels seen before obstruction. In animals with bilateral ureteral obstruction, proximal intratubular pressures are initially twofold higher (11, 14) than those seen in rats with UUO (Fig. 12-1). By 24 hours, the levels of intratubular pressure have fallen but not back to the baseline (14, 15). At this time, glomerular capillary pressure is no different from preobstruction values. Thus, in this setting, high intratubular pressures contribute significantly to the decrease in GFR.

Figure 12-1 Pressure in proximal renal tubules (PT) before, during, and after release of complete obstruction of one ureter (UUO), both ureters (BUO), or single nephrons (SNO). BUO, bilateral ureteral obstruction; SNO, single-nephron obstruction; UUO, unilateral ureteral obstruction.

Changes in Renal Blood Flow

Ureteral obstruction causes a transient increase in renal blood flow (16). Decreased resistance of the afferent arteriole accounts for the increase in blood flow to the unilaterally obstructed kidney (16, 17). This phenomenon is observed in both the denervated and the isolated perfused kidney, suggesting that this hyperemic phase is mediated through an intrarenal mechanism. Measurements of the distribution of blood flow during this phase indicate that inner cortical blood flow is increased (18, 19, 20). There is a progressive decrease in blood flow to the inner medulla during ureteral obstruction (21). This increase in renal blood flow may represent a hemodynamic response intended to maintain GFR. The increase in renal blood flow and afferent arteriolar dilatation leads to an increase in glomerular capillary pressure. This response maintains GFR at approximately 80% of preobstruction values despite the substantial increase in proximal tubular pressure. The mechanism underlying this response involves a signal generated at the single-nephron level because a wax plug placed in the proximal tubule generates an identical hemodynamic response in a single glomerulus. Tanner (22) suggested that the fall in afferent arteriolar resistance was caused by tubular-glomerular feedback related to interrupting acutely distal delivery of tubular fluid to the macula densa. Ichikawa (23), however, demonstrated that glomerular blood flow does not rise if proximal tubular pressure is maintained in the normal range in
the face of tubule blockade, suggesting that the altered glomerular hemodynamics are a result of intratubular dynamics rather than cessation of distal delivery of tubule fluid. The transient increase in renal blood flow after ureteral obstruction can be prevented by the administration of inhibitors of prostaglandin synthesis such as indomethacin (24). Thus, vasodilator prostaglandins, such as prostaglandin E2 and prostacyclin, may account for this initial vasodilator effect. At this time interval, the renal vascular bed is particularly resistant to vasoconstriction induced by either electrical stimulation of renal nerves or an infusion of catecholamines. In addition, autoregulation of renal blood flow is impaired, suggesting a prominent vasodilating influence following the onset of ureteral obstruction. Usually the increase in blood flow following obstruction peaks at about 2 to 3 hours.

In a second phase, approximately 3 to 5 hours after the onset of obstruction, renal blood flow starts to decline, while ureteral pressure continues to increase. In part, this may be a consequence of augmented renal resistance owing to increased interstitial pressure. In this phase, ureteral pressure starts to fall toward control values, and renal plasma flow continues to decline, reaching about 30% to 50% of control values by 24 hours (25, 26). This vasoconstrictive response of the kidney to UUO results predominantly from an increased resistance of afferent arterioles.

In animals with bilateral ureteral obstruction, the changes in renal hemodynamics are similar to those seen following UUO. There also is an initial hyperemic phase (14, 16) that is blocked by cyclooxygenase inhibitors (24), and the decline in GFR thus is secondary to a rise in intratubular pressure. Renal plasma flow falls progressively and is similar at 24 hours to that seen after UUO, although afferent arteriole resistance may not increase as much. As a result of the persistently high proximal tubular pressure and decline in renal plasma flow, it would be expected that the decline in GFR would be greater after bilateral ureteral obstruction than after UUO. However, this is not the case and may reflect the effect of a higher intraglomerular capillary pressure and greater number of filtering nephrons before and after release of obstruction of 24 hours’ duration in rats with bilateral ureteral obstruction than in those with UUO (27).

Changes in the Ultrafiltration Coefficient

After ureteral obstruction, GFR falls to a greater extent than renal plasma flow (9). Thus, the filtration fraction decreases. This may reflect preferential constriction of the preglomerular blood vessels because this would lower both blood flow and glomerular capillary pressure, thus resulting in a greater decrement in GFR than in blood flow. Alternatively, it is suggested that there is either diversion of blood to nonfiltering areas of the kidney or a reduced area available for filtration per glomerulus. That the latter occurs is suggested by the finding that Kf values in rats with ureteral obstruction are lower than those typically obtained in normal rats (28).

In summary, the fall in single-nephron GFR in obstruction is caused by a decrease in net hydrostatic pressure across the glomerular capillary wall. The fall in net hydrostatic filtration pressure initially is caused by an increase in intratubular pressure. After 24 hours of obstruction, the main mechanism responsible for the decrement in net hydrostatic pressure across the glomerular capillary wall is a fall in intraglomerular pressure. In animals with bilateral ureteral obstruction, both a persistent increase in intratubular pressure and a decrease in intraglomerular pressure contribute to the decrease in net hydrostatic pressure across glomerular capillaries. There also is evidence that Kf is decreased. The greater decrease in total kidney GFR than in single-nephron GFR after 24 hours of obstruction results from the fact that some nephrons cease to function during the period of obstruction.


After complete ureteral obstruction in the rat, GFR reaches 2% of control values by 48 hours and remains at this low level. Renal plasma flow also declines but to a lesser extent (25). The effects of partial chronic obstruction of the ureter depend on both the degree and the duration of the obstruction. Whole-kidney GFR may be reduced to one-third of control values 2 to 4 weeks following partial ureteral obstruction in the rat (29). Single-nephron GFR, however, is reduced by only 20% of control levels, suggesting that the decline in whole-kidney function is a result of a loss in the number of functioning nephrons not accessible to micropuncture, that is, juxtamedullary nephrons (30).

Rats with partial obstruction of 2 to 4 weeks’ duration have a 30% decrease in Kf. GFR and single-nephron plasma flow are maintained near normal because of an increase in glomerular capillary pressure secondary to a greater decrease in afferent than efferent arteriolar resistance. This vasodilatation is prostaglandin mediated,
and indomethacin administration increases both afferent and efferent arteriolar resistance and causes a decline in single-nephron GFR (31).


Experimental studies suggest that the vasoconstrictors angiotensin II and thromboxane A2 play a central role in the changes in plasma flow per nephron and single-nephron GFR seen after obstruction. Inhibition of thromboxane A2 synthesis in rats with ureteral obstruction increases plasma flow per nephron, owing to decreased vasoconstriction of both afferent and efferent arterioles (29). Thromboxane also may decrease Kf through mesangial cell contraction and a decrease in the surface area available for filtration. Although infusion of angiotensin II into normal animals increases net filtration pressure, presumably because of greater vasoconstriction of the efferent than the afferent arteriole, blockade of angiotensin II formation after relief of obstruction increases GFR (29). This increase in GFR may result from a greater filtering surface area, because angiotensin II causes mesangial cell contraction and therefore can reduce the total glomerular capillary area available for filtration. In addition, angiotensin II decreases plasma flow per nephron, which also contributes to the fall in single-nephron GFR. The central and critical role of these two vasoconstrictors in modulating postobstructive renal hemodynamics is illustrated by the fact that rats pretreated with both angiotensin-converting enzyme (ACE) and thromboxane synthase inhibitors, before obstruction, demonstrate almost normal renal function after release of obstruction (32).

Vasodilator prostaglandins, produced in increased amounts by the obstructed kidney, may prevent further decrements in GFR by antagonizing the vasoconstrictive effects of thromboxane A2 and angiotensin II. Indeed, it has been demonstrated that after release of obstruction in rats, in the setting of prior inhibition of the thromboxane synthase, administration of inhibitors of the cyclooxygenase causes a marked decrease in whole-kidney GFR and renal plasma flow (31).

Atrial natriuretic peptide (ANP), which can cause preglomerular vasodilatation and postglomerular vasoconstriction and increase Kf, are higher in rats with bilateral ureteral obstruction than in rats with UUO (33). ANP antagonizes the vasoconstrictive effects of angiotensin II, raising the possibility that the elevated levels of endogenous ANP in animals with bilateral ureteral obstruction minimize the renal vasoconstriction that occurs compared with animals with UUO.

An interstitial leukocyte infiltrate, predominantly macrophages, is an early event following ureteral obstruction. This begins to increase as early as 4 to 12 hours after ureteral obstruction and continues to increase over the course of days thereafter. By 4 days after left ureteral ligation, there is a 20-fold increment in the renal cortical macrophage number in the obstructed kidney versus either the contralateral unobstructed kidney or normal kidneys from age-matched, sham-operated animals (34). The signal for renal leukocyte recruitment immediately after ureteral obstruction is predominantly macrophage specific and appears to plays a key role in the acute functional changes after ureteral obstruction (35).


The degree of recovery of GFR after release of ureteral obstruction depends on the severity and duration of the obstruction. After release of a 2-week complete ureteral obstruction in the dog, GFR in the postobstructed kidney averages 25% of ipsilateral control values and 16% of concurrent values for the contralateral kidney, the latter having undergone a compensatory increase in GFR (36). Subsequently, the GFR of the postobstructed kidney increases, and the GFR of the normal kidney falls, stabilizing at about 2 months after the release of obstruction. However, GFR does not return to normal in the postobstructed kidney, remaining approximately 50% below the value obtained for the contralateral kidney at 2 years. The changes in effective renal plasma flow mirror the changes seen in GFR.

In rats, a permanent decrease in GFR occurs if ureteral obstruction has been present for >72 hours. After obstruction lasting <30 hours, recovery of whole-kidney GFR is complete, although the normalization in GFR may not be a consequence of homogeneous recovery in single-nephron GFR for all nephrons (37). When single-nephron GFR and the number of filtering nephrons are determined using a modification of Hansen’s technique, only 85% of the nephrons filter in the postobstructed kidney (37), suggesting the normalization of whole-kidney GFR occurs at the expense of hyperfiltration (increase in single-nephron GFR) in the remaining functional nephrons (Fig. 12-2). There appears to be a permanent decrement in the total number of functional nephrons.

Figure 12-2 SNGFR in SUP and JM nephrons of rats 8 and 60 days after release of UUO of 24 hours’ duration. The SNGFR values for the POK were significantly greater (asterisk) than those of the contralateral kidney. JM, juxtamedullary; POK, postobstructed kidney; SNGFR, single-nephron glomerular filtration rate; SUP, superficial; UUO, unilateral ureteral obstruction.

The permanent loss of nephrons is likely to be a consequence of fibrosis resulting from renal ischemia and the infiltration into the kidney of biologically active macrophages. The long-term significance of this on the development of significant CKD in adults is unclear particularly if the period of obstruction has been short. However, obstruction to the developing kidney either prenatally or in childhood appears to have important effects on renal function later in adult life even with effective relief of the obstruction (38).


Urinary tract obstruction results in altered renal handling of electrolytes and changes in the regulation of water excretion with a decreased ability to concentrate the urine. The degree and nature of the tubular defects after obstruction depend in part on whether the obstruction is bilateral or unilateral as a result of the dissimilar hemodynamic responses, different intrinsic changes within the nephron, and differences in extrinsic factors (e.g., volume expansion and accumulation of natriuretic substances in bilateral obstruction).

Sodium and Water Handling

In spite of a decrease in GFR and hence in the filtered load of sodium, the excretion of sodium by the postobstructed kidney of rats with UUO is similar to that of the contralateral kidney (39). Thus, fractional sodium excretion is greater from the postobstructed than from the contralateral kidney. Similar findings have been reported in the dog and in humans after more prolonged periods of obstruction. These findings indicate significant changes in the tubular reabsorption of sodium and water by the previously obstructed kidney. Changes in intravascular volume may affect the absolute and fractional excretion of salt and water by the postobstructed kidney. Absolute sodium excretion after release of UUO is reduced in rats with volume depletion studied under anesthesia when compared with awake rats. In contrast, expansion of the extracellular fluid (ECF) volume with saline solution increases both absolute and fractional sodium excretion. These increases are greater in the postreleased kidney than in the contralateral untouched kidney.

The release of bilateral ureteral obstruction results in a different quantitative excretion of salt and water than what occurs after release of UUO. There is a dramatic increase in the absolute amount of sodium and water excreted in the urine after release of bilateral ureteral obstruction in humans (40) and experimental animals (41, 42), resulting in the so-called postobstructive diuresis. The differences in salt and water excretion after release of bilateral ureteral obstruction and UUO may result from accumulation of osmolytes such as
urea and the expansion of the ECF volume during the period of bilateral ureteral obstruction. In addition, the circulating levels of ANP are significantly greater in rats with bilateral ureteral obstruction than in those with unilateral obstruction (33).

Urinary Concentration

Patients with partial obstruction of the urinary tract or patients after relief of partial or complete urinary obstruction have impaired renal concentrating capacity (43), which may take some months to recover following the release of obstruction.

After relief of unilateral obstruction of 24 hours’ duration in rats, the urine osmolality from the postobstructed kidney seldom exceeds 400 mOsm/kg H2O compared with approximately 2,000 mOsm/kg H2O in the contralateral untouched rat kidney.

The urinary concentrating defect may be explained by both a decreased hypertonicity of the medullary interstitium and a failure of the cortical collecting duct to respond to the action of antidiuretic hormone (ADH). The later may result from a decrease in expression of aquaporin-2 following obstruction to the urinary tract (44).

Obstruction results in a permanent decrease in the number of juxtamedullary nephrons (37). As these have the longest loops of Henle and are responsible for the reabsorption of solutes and the creation of a hypertonic medulla, their loss causes a permanent defect in the concentrating ability of the postobstructed kidney, although this is not as marked as that seen in the acute stages of obstruction.

In addition to the mechanisms described above, following release of bilateral ureteral obstruction, the osmotic effect of solutes retained during the period of obstruction contributes to the generation of isotonic urine after relief of bilateral ureteral obstruction.

Urinary Acidification

In humans (43) and experimental animals (45, 46), acid excretion is impaired after the release of obstruction, and returns to normal after some time (months). Studies in experimental animal models of urinary tract obstruction (46) as well as in patients (43) suggest there is a form of distal renal tubular acidosis with an inability to lower the urine pH to normal minimum values in response to acidemia or acid loading.

Potassium Excretion

At any given level of GFR, the fractional excretion of potassium is less in patients with obstructive uropathy than in a comparable group of patients with renal insufficiency caused by a variety of renal diseases (Fig. 12-3). There is a hyperkalemic hyperchloremic acidosis (47) which may be explained at least in part by (a) a deficiency of aldosterone secretion probably secondary to diminished production of renin by the kidney (hyporeninemic hypoaldosteronism), (b) a defect in renal hydrogen ion secretion with an inability to lower pH of the urine maximally in the presence of systemic acidosis and decreased urinary excretion of both ammonium and titratable acid (type 4 distal renal tubular acidosis), (c) a combination of these two defects, or (d) a decreased sensitivity of the distal tubule to the action of aldosterone on potassium secretion.

Excretion of Divalent Cations and Phosphate

Experimental studies have demonstrated a number of changes to the way the kidney handles divalent cations and phosphate following obstruction (48). Fractional excretion of calcium is decreased after release of unilateral obstruction but magnesium excretion increases following release of bilateral or UUO and may result in profound hypomagnesemia.

The reabsorption of phosphate by the postobstructed kidney depends on both the duration of the obstruction and whether the obstruction is bilateral or unilateral. After release of UUO, altered phosphate excretion results primarily from altered renal hemodynamics, and following release of bilateral ureteral obstruction, phosphate excretion is modulated to a large extent by extrarenal factors, mainly the serum levels of phosphate. The obstructed kidney can still respond to exogenous parathyroid hormone administration with an increase in urine phosphate and cyclic 3′5′-adenosine monophosphate excretion, but the magnitude of the response is less in the postobstructed kidney than in the contralateral kidney.

Figure 12-3 Relation of FEK to GFR under baseline conditions. The area inside the broken line depicts the normal adaptive increase in fractional potassium excretion observed with a chronic reduction in GFR. These data were obtained from 14 normokalemic controls (triangles) with different GFRs. Each patient (circle and square symbols) had a baseline FEK lower than that expected for the corresponding GFR. Circles denote patients with distal renal tubular acidosis (group I); open squares represent patients with hyperkalemic metabolic acidosis owing to selective aldosterone deficiencies (group II). FEK, fractional excretion of potassium; GFR, glomerular filtration rate. (From Batlle DC, Arruda JAL, Kurtzman NA. Hyperkalemic distal renal tubular acidosis associated with obstructive uropathy. N Engl J Med. 1981;304(7):373-380, Copyright © 2017 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.)

The Effects of Ureteral Obstruction on Renal Structure

Following ureteral obstruction, a number of factors result in morphologic changes to the kidney, including the increase in ureteral pressure, the decrease in renal blood flow (ischemia), an invasion by macrophages and lymphocytes, and bacterial infection. The subsequent macroscopic structural changes that are found in the kidney depend on both the duration and degree of the obstruction.

Following acute complete obstruction initially, there is pelvicalyceal dilation, renal enlargement, and edema (Fig. 12-4, left panel). Microscopically, tubular dilation develops that predominantly affects the collecting duct and distal tubular segments (49), though cellular flattening and atrophy of proximal tubular cells can also occur. Glomerular structures are usually preserved initially, although Bowman’s space may be dilated and may contain Tamm-Horsfall protein. Ultimately, some periglomerular fibrosis may develop.

In chronic partial obstruction a grossly hydronephrotic kidney develops with a widely dilated renal pelvis, with the renal papilla either flattened or hollowed out. The first structures to be affected are the ducts of Bellini. Subsequently, other papillary structures are damaged. Ultimately, there is an encroachment on renal cortical tissue, which in advanced cases may be reduced to a thin rim of renal tissue surrounding a large saccular ureteral pelvis (Fig. 12-4, right panel).

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Nov 17, 2018 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Obstructive Nephropathy: Pathophysiology and Management
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