Link between obstructive uropathy and acute kidney injury

Abstract

Obstructive uropathy represents a major risk of acute kidney injury. From an epidemiological point of view, it is responsible for 5% to 10% of cases of acute renal failure and 4% of cases of end-stage kidney disease. Although obstructive uropathy is a recognized disease, there is a significant lack of detailed research on this topic from both a nephrological and urological perspective. The majority of published research focuses on the pathophysiology of the topic and neglects a comprehensive analysis of diagnostic and treatment approaches supported by current data. In this context, it is crucial to assess the overall hemodynamic status, especially in the presence of urosepsis. Once clinical stability is assured, it is important to focus on symptom management, usually by controlling pain. Ultimately, it is crucial to decide immediately whether the patient should receive a prompt urinary diversion. Urinary diversion is an essential part of the treatment of obstructive uropathy and should be initiated promptly and without unnecessary delay once the diagnosis has been confirmed. Functional recovery of the obstructed kidney after decompression of the urinary tract depends on the degree of obstruction, the duration of the obstruction and the presence of a concomitant urinary tract infection. The timing and proper treatment of this condition determines the recovery of kidney function after an obstruction and prevents the development of chronic kidney disease. In this editorial, we emphasized the pathophysiological role and clinical significance of obstructive uropathy in the context of acute kidney injury.

Key Words: Obstructive uropathy; Acute kidney injury; Chronic kidney disease; Kidney stones; Hydronephrosis

Core Tip: Obstructive uropathy is a common cause of acute kidney injury. An accurate initial assessment is crucial to identify patients who may benefit from early urinary diversion and to avoid potential complications. The initial evaluation must include a physical examination, a thorough medical history, laboratory tests, and imaging studies. The treatment includes surgical and pharmacological approaches, depending on the underlying causes of the acute kidney injury, which can be multifactorial. Further research is needed to develop targeted interventions to improve patient outcomes based on multidisciplinary evaluation.

INTRODUCTION

Obstructive uropathy is a disorder of the urinary tract that can be structural or functional and is caused by an obstacle to urine flow. Although obstruction can cause a variety of symptoms, the most common are pain in the lower abdomen, acute urinary retention, and difficulty urinating. Both acute and chronic conditions are possible. Obstructive uropathy can often lead to acute kidney injury (AKI), causing 5% to 10% of all cases of acute renal failure[1]. However, in older people (over 60 years), it can occur in up to 55% of AKI cases[2].

Obstruction of the urinary tract significantly impairs renal function by causing damage due to ischemia and inflammatory processes associated with severe fibrosis. This disease is characterized by a disturbance in the regulation of fluid, electrolyte, and acid-base balance within the renal tubules. Acute renal dysfunction due to obstructive nephropathy leads to metabolic acidosis, hyperkalemia, uremia, and anuria. After dehydration, polyuria may manifest itself. The typical manifestation is acute urinary retention. Diagnosis requires a thorough history that includes changes in urination and urinary urgency, enuresis, previous urinary tract infections, hematuria, renal lithiasis, previous diuretic treatment, and constipation. Imaging studies include tomography or ultrasound to visualize the hydronephrosis. Treatment includes removal of the obstructed urinary tract, supportive care, correction of metabolic abnormalities, and initiation of renal replacement therapy if necessary.

This condition has a significant impact on the health and mortality rate of affected individuals. Although the prognosis for recovery is often positive, the significance of this event often seems to be underestimated in the fields of nephrology and urology. This misconception stems from the false belief that once the urinary tract is no longer blocked, kidney function is fully restored. This can lead to serious renal complications. The article of Pérez-Aizpurua et al[3] provided a comprehensive analysis of the epidemiology, incidence, pathophysiologic causes, diagnosis, and management of AKI caused by obstructive nephropathy.

ETIOLOGY

Obstructive uropathy can manifest at any age, from the prenatal period to adulthood, and is caused by chronic obstruction of the urinary tract, which may be associated with hydronephrosis (i.e. dilation of the urinary tract)[1].

Obstructive uropathy can be divided into three types based on the site of the obstruction: (1) Intrarenal: Kidney stones, infundibular stenosis as a result of infection or stones, urothelial tumors, blood clots; (2) Postrenal-intravesical: Ureterohydronephrosis that develops proximal to the site of obstruction. There are intrinsic causes such as ureteral stones, ureteral tumors, obstruction of the pelvic-ureteral joint and extrinsic causes such as retroperitoneal masses or fibrosis or compression by gynecological cancer, bladder tumors, or prostate cancer with infiltration of the trigone; and (3) Postvesical: Ureteric malformation, prostatic causes, and contractile disorders of the bladder. This pathology is characterized by bilateral obstructive uropathy with bilateral ureterohydronephrosis[2,3].

In addition, obstructive uropathy can be classified according to the underlying cause (congenital or acquired), the duration (acute or chronic), the degree (partial or complete), and the localization (unilateral or bilateral)[4].

STRUCTURAL AND FUNCTIONAL ALTERATION IN OBSTRUCTIVE UROPATHY

Obstructive nephropathy is characterized by severe vasoconstriction and profoundly alters all components of glomerular function. The change in glomerular function depends on the duration and type of obstruction (unilateral or bilateral) and whether the obstruction persists or not. Three different phases follow the onset of the obstructive uropathy: Phase I (0-1.5 h), which is characterized by an increase in ureteral pressure and renal blood flow (RBF), possibly due to predominant preglomerular vasodilation; Phase II (1.5-5 h), which is characterized by postglomerular vasoconstriction secondary to an increase in ureteral pressure and a decrease in RBF; and Phase III (5-18 h), which is characterized by a decrease in ureteral pressure and RBF and may be explained by preglomerular vasoconstriction[3]. This afferent vasodilation is mediated by an increase of vasodilator hormones such as prostaglandins, a reduced sodium concentration at the macula densa, and significant hemodynamic alterations[4,5]. In phase III, RBF decreases further, falling by 30% of preobstructive levels, with high plasma angiotensin II levels after 15 h of unilateral ureteral obstruction (UUO), consistent with other studies showing persistent active vasoconstriction. The mechanism underlying phase III is thought to be continuous vasoconstriction localized predominantly in the preglomerular vasculature[4].

UUO in rats for 24 h significantly increased afferent arteriolar resistance and decreased afferent arteriolar blood flow[4]. These studies highlighted the critical role of afferent arteriolar vasoconstriction in decreasing the glomerular filtration rate (GFR) during the established phase of obstruction. In response to UUO, intrarenal mechanisms cause the late preglomerular vasoconstriction. Therefore, in the second and third phase beyond the progressive reduction of RBF, GFR, and renal tissue perfusion the reduction of oxygen delivery to the renal cortex and to the renal medulla leads to a gradual loss of the capillary network in the kidney. This mechanism increases apoptosis and stimulation of cell infiltration in the renal parenchyma[6]. Numerous intrarenal vasoactive compounds such as angiotensin II and thromboxane A2 may be involved in active vasoconstriction by increasing the inflammatory process, the matrix protein deposition, and the development of progressive interstitial fibrosis by prostaglandin E2 blockade, COX-2 inhibition, angiotensin II converting enzyme inhibitors, angiotensin II receptor blockade, suppression of thromboxane A2 production, kallikrein inhibitors, and endothelin. Endothelin A receptor blockade contributes significantly to the reduction of RBF and GFR[7].

Another important structural change in obstructive uropathy is the progressive development of atubular glomeruli, which appears to play an important role in obstructive nephropathy. Forbes et al[8] used histomorphometry to investigate the formation of atubular glomeruli in adult mice affected by obstructive uropathy. In this experiment, they showed that after only 14 days, destruction of the glomerulo-tubular junction and the formation of atubular glomeruli had developed in 80% of the nephrons.

The glomerulo-tubular junction became atrophic due to autophagy and apoptosis, while at the same time the Bowman capsule was remodeled to form atubular glomeruli. During this deterioration, the epithelial cells in the urinary pole transformed into a mesenchymal phenotype and expanded to cover the capsule. At the same time, perfusion of the atubular glomeruli was maintained, although renin-positive cells along the afferent arterioles increased significantly[9]. These events suggested that both degenerative and regenerative processes were activated in response to the formation of atubular glomeruli after UUO and that the glomerular and tubular epithelium plays an important role in progressive renal injury[3,10].

OBSTRUCTIVE UROPATHY TREATMENT

Obstructive uropathy has a remarkable clinical significance and leads to both acute and chronic renal damage. This entity is partially and relatively preventable if the obstructive cause is treated quickly and successfully.

The location and cause of the urinary tract obstruction determine the surgical method used. It is advisable to postpone definitive urological surgery until the patient’s medical condition is stable and urgent decompression has been successfully performed. Rapid emptying of the bladder can lead to hematuria ex vacuo. Relief of the chronically distended bladder, which is associated with a fragile bladder wall and damage to the capillaries, results in visible bleeding in about 10% of cases[11].

In severe renal failure due to obstruction or in the presence of an infected obstructed kidney, resuscitation and emergency drainage are of paramount importance. Preliminary measures such as percutaneous nephrostomy or the insertion of a bladder catheter usually precede any corrective treatment performed later.

Percutaneous nephrostomy is an established interventional procedure that temporarily drains urine from the obstructed kidney. This procedure has been shown to improve kidney function, but is also associated with significant morbidity, which can have a negative impact on quality of life. Nevertheless, it has the potential to be life-saving. A study was conducted on 140 patients with obstructive nephropathy due to advanced cancer. The authors looked at survival rates at different time points. They determined that survival rates varied between 4 months and 31 months, and it was major if it was associated with an increase of renal function[12]. However, studies have shown that in obstructive nephropathy caused by malignant tumor disease, conservative management instead of invasive procedures such as nephrostomy or retrograde urethral stenting resulted in a similar survival rate[13].

In a multicenter, retrospective study, Artiles Medina et al[14] showed that the presence of AKI has a detrimental effect on the long-term outcomes of patients who underwent percutaneous nephrostomy for obstruction. The main cause of obstructive uropathy in adults was usually cancer, followed by the presence of urinary stones and other factors. In addition, a considerable number of patients (78%) suffer from AKI together with an infection. After the insertion of a percutaneous nephrostomy, 56.8% of these patients were able to recover in the short term. In addition, an overall mortality rate of 34% was found, with the highest mortality rate observed in cases where the obstruction was caused by cancer (52%).

In their review, Pérez-Aizpurua et al[3] emphasized the importance of assessing the timing of urinary diversion. They differentiated between the urgent need for urine diversion and other cases that can be postponed. Urgent urinary diversion is urgent in cases with high-risk infectious complications such as urosepsis and pyonephrosis as well as in the presence of a single kidney, bilateral upper tract obstruction, previously established renal dysfunction, or hyperkalemia. In addition, bacteremia without concomitant sepsis does not need to be drained immediately but requires urgent treatment; it can be safely delayed by 6-8 h[15]. After decompression, the use of alpha-1 receptor blockers is recommended, as these receptors play a role in the regulation of the bladder, urethra, and prostate[16,17]. Pain in obstructive uropathy is caused by increased pressure in the collecting system and stretching of the ureteral wall and renal capsule. Medications used to treat the discomfort caused by acute renal colic include nonsteroidal anti-inflammatory drugs (NSAIDs), narcotic analgesics, and corticosteroids[18]. NSAIDs have been shown to reduce overall systemic pressure by targeting the inflammatory cause of pain[19,20]. It is important to consider the most appropriate pain treatment depending on the patient’s clinical profile, especially in patients with impaired renal function who should avoid taking NSAIDs[21].

CONCLUSION

AKI due to obstructive uropathy is a serious condition that must be recognized and treated immediately to prevent permanent damage and consequences. Timely detection and removal of the obstruction is crucial to prevent AKI and facilitate recovery. Further studies are needed to provide appropriate biomarkers to monitor this condition and to develop effective drug and surgical therapies to treat this insidious cause of AKI.