Prerenal and Intrinsic Acute Kidney Injury Distinguished by A Metabolic Signature
- 1Department of Cellular Biology & Anatomy, Medical College of Georgia, Augusta University, August, GA, 30912
- 2Charlie Norwood VA Medical Center, Augusta, GA, 30904
Abstract
Acute kidney injury (AKI) is traditionally classified into three major categories according to its underlying etiology: prerenal AKI due to reduced renal perfusion, intrinsic AKI resulting from structural damage to the kidney, and postrenal AKI caused by urinary tract obstruction.Among these, prerenal AKI has long been regarded as a functional and reversible disorder that resolves following restoration of renal perfusion.Consequently, mechanistic investigations have largely focused on intrinsic and obstructive AKI, but not on prerenal AKI.Nevertheless, some important questions remain unresolved and have direct clinical implications.First, how can prerenal AKI be reliably distinguished from intrinsic AKI?Although both conditions present with reduced glomerular filtration rate (GFR) and elevated blood urea nitrogen (BUN) and serum creatinine levels, their underlying pathophysiology and clinical management differ substantially, and an accurate etiologic diagnosis is therefore essential, as inappropriate treatment may delay recovery or even exacerbate kidney injury(1, 2).Current diagnostic tools, including urinary kidney injury markers such as kidney injury molecules-1(KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) have shown promise in differentiating intrinsic tubular injury from prerenal AKI, but considerable individual variability has limited their adoption as definitive diagnostic standards(1, 3-5).Second, is prerenal AKI truly a benign, transient condition without any long-term consequences?Experimental study has reported transient systemic inflammatory responses in prerenal AKI(6).Furthermore, clinical studies demonstrated that prerenal AKI patients still have chances to develop major adverse kidney events(7) and even patients with mild and short-duration AKI (stage 1 with renal function recovery within 1 day, including prerenal cases) have an increased risk of developing chronic kidney disease (CKD)(8).Whether these adverse outcomes arise from transient renal hypoperfusion itself or instead reflect the severity of the underlying systemic insult remains an important unresolved question.
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BibTeX
@article{wei2026prerenal,
title = {{Prerenal and Intrinsic Acute Kidney Injury Distinguished by A Metabolic Signature}},
author = {Qingqing Wei and Zheng Dong},
journal = {American journal of physiology. Renal physiology},
year = {2026},
month = oct,
doi = {10.1152/ajprenal.90002.2026},
url = {https://doi.org/10.1152/ajprenal.90002.2026},
note = {Public domain},
}
RIS
TY - JOUR
TI - Prerenal and Intrinsic Acute Kidney Injury Distinguished by A Metabolic Signature
AU - Qingqing Wei
AU - Zheng Dong
PY - 2026
DA - 2026/10/12
JO - American journal of physiology. Renal physiology
DO - 10.1152/ajprenal.90002.2026
UR - https://doi.org/10.1152/ajprenal.90002.2026
AB - Acute kidney injury (AKI) is traditionally classified into three major categories according to its underlying etiology: prerenal AKI due to reduced renal perfusion, intrinsic AKI resulting from structural damage to the kidney, and postrenal AKI caused by urinary tract obstruction.Among these, prerenal AKI has long been regarded as a functional and reversible disorder that resolves following restoration of renal perfusion.Consequently, mechanistic investigations have largely focused on intrinsic and obstructive AKI, but not on prerenal AKI.Nevertheless, some important questions remain unresolved and have direct clinical implications.First, how can prerenal AKI be reliably distinguished from intrinsic AKI?Although both conditions present with reduced glomerular filtration rate (GFR) and elevated blood urea nitrogen (BUN) and serum creatinine levels, their underlying pathophysiology and clinical management differ substantially, and an accurate etiologic diagnosis is therefore essential, as inappropriate treatment may delay recovery or even exacerbate kidney injury(1, 2).Current diagnostic tools, including urinary kidney injury markers such as kidney injury molecules-1(KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) have shown promise in differentiating intrinsic tubular injury from prerenal AKI, but considerable individual variability has limited their adoption as definitive diagnostic standards(1, 3-5).Second, is prerenal AKI truly a benign, transient condition without any long-term consequences?Experimental study has reported transient systemic inflammatory responses in prerenal AKI(6).Furthermore, clinical studies demonstrated that prerenal AKI patients still have chances to develop major adverse kidney events(7) and even patients with mild and short-duration AKI (stage 1 with renal function recovery within 1 day, including prerenal cases) have an increased risk of developing chronic kidney disease (CKD)(8).Whether these adverse outcomes arise from transient renal hypoperfusion itself or instead reflect the severity of the underlying systemic insult remains an important unresolved question.
SN - 1931-857X
SN - 1522-1466
ER -