Is the concept of acute renal success still valid in the setting of ischemic acute kidney injury (Acute Kidney Injury, AKI) and what was historically called Acute Tubular Necrosis (ATN)?

From the Guidelines

The concept of acute renal success remains valid in the setting of ischemic acute kidney injury (AKI) and what was historically called Acute Tubular Necrosis (ATN), as it refers to the adaptive responses that occur during AKI to preserve tubular integrity and prevent further damage. According to the consensus report of the Acute Disease Quality Initiative (ADQI) 16 workgroup 1, acute renal success is accomplished through tubuloglomerular feedback mechanisms that reduce glomerular filtration rate (GFR) in response to tubular injury, helping to match filtration to the kidney's compromised reabsorptive capacity.

During ischemic injury, these protective mechanisms include afferent arteriolar vasoconstriction, mesangial cell contraction, and tubular backleak of filtrate, all of which reduce energy demands on damaged tubular cells. While these responses help preserve kidney tissue in the short term, prolonged activation can contribute to persistent kidney dysfunction. Understanding this concept is clinically important because it explains why aggressive fluid resuscitation alone may not immediately restore kidney function after an ischemic insult - the kidney is actively reducing filtration as a protective measure.

Treatment should focus on addressing the underlying cause of ischemia, maintaining adequate perfusion pressure, avoiding nephrotoxins, and providing supportive care while allowing these adaptive mechanisms to resolve naturally as tubular repair occurs. The ADQI 16 workgroup also proposes a framework for acute kidney disease (AKD) that includes stages 0A, 0B, and 0C, which represent different levels of kidney damage and functional loss after an episode of AKI 2, 3. This framework highlights the importance of monitoring and follow-up care for patients with AKI, even after apparent recovery, to prevent long-term kidney damage and other adverse outcomes.

Key considerations in the management of AKI and AKD include optimizing haemodynamic and volume status, avoiding nephrotoxic medications, and providing supportive care to facilitate renal recovery 4. By prioritizing these measures and recognizing the adaptive responses that occur during AKI, clinicians can improve outcomes and reduce the risk of long-term kidney damage and other morbidities.

Some of the key points to consider in the management of AKI and AKD include:

• Monitoring serum creatinine levels and urine output to assess renal function and detect any signs of worsening kidney damage
• Avoiding nephrotoxic medications and minimizing the use of contrast agents
• Optimizing haemodynamic and volume status to maintain adequate perfusion pressure and prevent further kidney damage
• Providing supportive care, such as dialysis or other renal replacement therapies, as needed to facilitate renal recovery
• Educating patients and their families about the risks and consequences of AKI and AKD, and the importance of follow-up care and monitoring to prevent long-term kidney damage and other adverse outcomes.

From the Research

Definition and Pathogenesis of Acute Kidney Injury (AKI)

• Acute kidney injury (AKI) is defined as the abrupt decline in glomerular filtration rate (GFR) resulting from ischemic or toxic injury to the kidney 5.
• The pathogenesis of AKI involves four major factors: decrease of glomerular capillary permeability, back-leak of glomerular filtrate, tubular obstruction, and intrarenal vasoconstriction 5.
• Acute tubular necrosis (ATN) is the leading cause of AKI in adults, secondary to ischemia and/or tubular toxicity 6.

Acute Tubular Necrosis (ATN)

• ATN is characterized by desquamation of tubular epithelial cells and hyaline intra-tubular deposits 6.
• The diagnosis of ATN is confirmed by a spontaneous improvement of AKI and an evocative clinical context 6.
• The prognosis of ATN is often severe, and despite functional recovery, the cellular repair is abnormal, leading to accelerated renal aging and increased susceptibility to nephrotoxicity 6.

Experimental Models and Treatment

• Experimental models of acute renal failure have been developed to study ischemic and toxic renal injury, but the results of clinical studies have been disappointing 7.
• Reactive oxygen species (ROS) may contribute to the initiation and maintenance of ATN, and may also participate in the recovery phase of ATN 8.
• Currently, there is no specific treatment for ATN, but regular monitoring of renal function and simple nephroprotection measures are recommended for patients who have experienced ATN 6.

Clinical Relevance

• The concept of acute renal success is still valid in the setting of ischemic AKI and ATN, as the goal of treatment is to prevent or ameliorate the severity of tubular injury and accelerate the recovery of established ATN 7, 5.
• The diagnosis and treatment of AKI and ATN require a comprehensive approach, taking into account the underlying causes and pathogenesis of the disease 5, 6.