AKI is diagnosed by a creatinine rise of ≥ 0.3 mg/dL within 48 hours, a rise to ≥ 1.5 times baseline within 7 days, or oliguria. According to the KDIGO system, it is classified into three stages based largely on creatinine1 levels and urine output, reflecting the inability to maintain electrolyte, acid–base, and/or water balance:
| Stage | Serum creatinine level | Urine output |
|---|---|---|
| 1 | 1.5–1.9 times baseline or an increase of ≥ 0.3 mg/dL (≥ 26.5 μmol/L) | < 0.5 mL/kg/h for 6–12 hours |
| 2 | 2.0–2.9 times baseline | < 0.5 mL/kg/h for ≥ 12 hours |
| 3 | 3.0 times baseline or an increase in serum creatinine to ≥ 4.0 mg/dL (≥ 353.6 μmol/L) or initiation of renal replacement therapy or, in patients < 18 years, a decrease in eGFR to < 35 mL/min per 1.73 m² | < 0.3 mL/kg/h for ≥ 24 hours or anuria for ≥ 12 hours |
This table is presented in Mercado et al.2 But these are merely generic manifestations of a broader derangement of kidney function we call AKI and do not refer to specific physiological mechanisms or etiologies. The paper divides etiologies into three classes: prerenal, intrinsic renal, and postrenal. These terms refer to anatomical and physiological relations rather than temporal ones.
Intravascular volume depletion3 decreases the volume returning to the heart, thereby lowering cardiac output (CO). Because hydrostatic pressure drives filtration within the glomerulus, prerenal AKI is often caused by volume depletion. Fluid loss or redistribution4 is most likely involved. Many prerenal causes act before the bulk of the nephron and are thus termed prerenal.
Damage to the glomerulus or tubule itself is a main cause of intrinsic renal pathology. Examples put forth include damage sustained from immune complexes associated with systemic illness,[^immune-complex] acute tubular necrosis (ATN), and acute interstitial nephritis (AIN).5 ATN mechanisms include ischemic or nephrotoxic injury: ischemic injury from hypovolemia or hypoperfusion, and nephrotoxic injury from endogenous and exogenous toxins associated with infection. AIN can be caused by a hypersensitivity reaction to certain medications.[^inflammatory-medications]
Postrenal etiologies consist of obstructions to urine flow, such as those caused by cervical cancer.
The concentration of ATP within the muscle fiber is around 4 µM. This is only enough to maintain full contraction for 1–2 seconds. To avoid complete depletion of ATP, rephosphorylation of ADP is necessary. Phosphocreatine (PPC), phosphorylated creatine, regenerates ATP from ADP. PPC has a higher ∆G than ATP, allowing the reaction to be coupled without being energetically unfavorable. (Some textbooks and most biology classes describe the chemical breakdown of a bond as an alteration that “releases energy.” This is simply untrue. Breaking a bond has never released any amount of energy in the history of reality as we know it, whereas forming a bond has. If breaking a bond has been part of a process that has “released energy,” it was because the energy released by forming the new bond exceeded the energy required to break the original bond, yielding excess energy, most likely in the form of heat.) Following PPC exhaustion, as the PPC concentration is merely around five times the ATP concentration, glycolysis proceeds to produce pyruvate and subsequently lactic acid for the rapid provision of ATP via lactic acid fermentation. Creatine is not naturally a stable protein and undergoes irreversible spontaneous cyclization to form creatinine. This is then filtered out of the blood through the glomerulus and excreted in urine. Hence, a higher concentration of serum creatinine indicates a lack of filtration and impaired kidney function. ↩︎
Mercado, M. G., Smith, D. K., & Guard, E. L. (2019). Acute Kidney Injury: Diagnosis and Management. American Family Physician, 100(11), 687–694. ↩︎
Fluid resuscitation may be indicated to correct fluid depletion. Isotonic crystalloids are recommended over colloids because of cost and efficacy. This is strange because colloids should have a theoretical advantage, being larger in size and therefore less likely to escape from the intravascular space. ↩︎
Nephrotic syndrome may lead to accidental filtration of albumin from the plasma and excretion in the urine, resulting in reduced plasma albumin. Consequently, lower oncotic pressure drives edema, causing fluid to accumulate in the interstitial tissues. This effectively reduces the amount of fluid in systemic circulation and, hence, intravascular volume. ↩︎
One must note that there is a difference between nephrotic and nephritic syndromes. Whilst nephritic syndrome is largely inflammatory in nature, nephrotic syndrome is caused by a wide variety of aberrations that share common ↩︎