AKI

Question 1

Pre-renal cause: Acute tubular necrosis (ATN)

Answer 1

ATN is the most common cause of AKI.

Causes of ATN: Renal ischemia (hypoperfusion), sepsis (release of mass inflammatory cytokines, ROS, and hypoperfusion), and nephrotoxins (causing direct tubular damage ).

Hypoperfusion may be induced by dehydration, burns, surgery, renal loss, bleeding, D&V, CCF, cirrhosis, systemic vasodilatation (sepsis), coagulopathy (DIC).

Drugs that cause ATN inc aminoglycosides, amphotericin B, radiocontrast, sulfa drugs, acyclovir, cisplatin, calcineurin inhibitors, IVIG. Haemoglobin and myoglobin cause renal vasoconstriction, tubular injury, nephropathy.

Pathophys:

1. initial phase (drop in GFR and risk in creatinine/urea)
   - systemic hypoperfusion leads to renal hypoperfusion. Renal medulla is most susceptible to hypoxia as medullary blood flow is relatively low in comparison to the cortex. Insufficient flow leads to medullary ischemia, resulting in tubulointerstitial injuries.
   - Poor renal perfusion activates tubuloglomerular feedback leading to arteriole vasoconstriction, backflow of glomerular filtrate, tubular obstruction
   - Other effects inc proximal Na+ reabsorption (in attempts to conserve Na+), release of adenosine, activation of sympathomimetic activity, activation of RAAS system (as there is more NaCl delivery to the macula densa which then activates afferent arteriole constriction) and ADH release, accumulation of reactive ox species, ATP depletion
2. Extension
   - continued hypoxia from sustained severe GFR reduction (1-2wks) occurs esp in corticomedullary junction, straight portion (S3) of the PCT and ascending limb of loop of Henle. Cells of outer medulla develop injury, necrosis, apoptosis. sloughing of epithelium and intratubular obstruction with cast formation (tubular obstruction affects a large number of nephrons which drain into that tubule)
   - this leads to inflammatory cascade response which further drops GFR. ATP depletion leads to necrosis.
   - this further perpetuates necrosis (inflamm mediators cause further vasoconstriction)
3. maintenance
   - cellular apoptosis, migration, proliferation and repair in attempts to maintain homeostasis, cellular and tubule integrity
   - mild improvement in renal function
4. recovery phase
   - recovery phase of ATN involves regeneration of tubular epithelium from continuation of maintenance phase. Can result in excess diuresis

Histopath: Denudation of renal tubular cells, effacement and loss of PCT brush border, flattening renal tubular cells due to PCT tubular dilatation, intratubular casts, sloughing off cells (leading to red casts).

Investigations:

• urinalysis may show hyaline casts, or muddy brown casts
• Fractional excretion of sodium (FENa) >2% favours ATN, <1% favours pre-renal disease
• urine Na: >40-50 suggests ATN (conserving Na+), <20mEq/L suggests pre-renal disease
• biomarkers to detect AKI: cystatin C, b2 microglobulin, KIM-1

Management: Ceasing ACE-I or ARB, IVFT, cease nephrotoxics

Sources: https://www.ncbi.nlm.nih.gov/books/NBK507815/

https://www.uptodate.com/contents/pathogenesis-and-etiology-of-ischemic-acute-tubular-necrosis