Acute tubular necrosis (ATN), phases of ATN

Acute parenchymal renal failure (acute tubular necrosis, ATN, ARF) is direct damage to the renal parenchyma, most commonly ischemic or toxic. ATN is usually associated with oliguria (diuresis < 500 ml/day), and brownish casts are often present in the urinary sediment.

ATN can develop from prerenal failure based on vasoconstriction with subsequent development of tubular necrosis; it can arise based on hypoxic-ischemic damage, toxic damage to tubular cells by drugs, contrast media, exogenous, and endogenous toxins.

Acute tubular necrosis – histological specimen

The prognosis of ATN is good, except for severe involvement with the formation of thrombi in the microcirculation leading to cortical necrosis. The mortality and morbidity of children with ARF is worse in newborns and children with multi-organ involvement. Renal functions in children with ATN who recover usually normalize. In some children, recovery of renal functions may take several days, in others several weeks. The recovery of renal functions may be accompanied by a polyuric phase, which is less common in children than in adults.

Etiopathogenesis

Ischemic ARF

Reduction of renal functions caused by ischemic damage to the tubules as a result of renal hypoperfusion (most commonly shock states) manifests as:

1. a decrease in blood flow (mainly through the cortex),
2. a reduction in the permeability of the capillary wall,
3. reflux of filtrate through the damaged tubular wall into the interstitium,
4. obstruction of the tubules.

Prolonged ischemia reduces the production of vasodilatory substances and stimulates the production of vasoconstrictors → deepening of ischemia → necrosis of tubular cells. This allows the reflux of filtrate through the necrotic epithelium back into the interstitium, making filtration ineffective; additionally, desquamated tubular cells can clog the lumen of the tubules → ↑ tubular pressure and stop glomerular filtration.

Nephrotoxic ARF (Nephrotoxic Damage or Severe TIN)

Nephrotoxic ARF can be caused by internal (endogenous) or external (exogenous) influences.

Exogenous influences include:

1. Antibiotics – aminoglycosides accumulating in the proximal tubule and causing the release of lysosomes → destruction; sulfonamides causing tubular obstruction by crystals; tetracyclines and amphotericin B,
2. Contrast media,
3. Heavy metals (Hg, Pb, etc.),
4. Chemotherapeutic agents – methotrexate; cisplatin – damages mitochondria, blocks ATPase; mitomycin,
5. Immunosuppressants – cyclosporine – intrarenal constriction of the afferent arteriole,
6. Organic solvents – ethylene glycol.

Endogenous influences include:

Intratubular precipitation of hemoglobin or myoglobin – rhabdomyolysis: crush syndrome, ischemic muscle damage, ketoacidosis, infection, cocaine.

Laboratory Findings

Excretory fraction of Na⁺ > 3%, osmolarity approaches plasma osmolarity.

Clinical Picture and Course

ARF persists even after the restoration of renal perfusion, whereas prerenal ARF can resolve immediately. The course can be divided into three phases. The first is the initial phase, when the insult occurs and it is still possible to prevent oliguria. The second phase is the phase of established ARF, where oliguria appears, lasting 7–14 days; this phase carries risks of: hyperhydration, ionic imbalance (especially hyperkalemia), acidosis, and uremic syndrome. The final phase is the repair phase, when functions gradually return and flow through the tubules is restored; the first diuresis → inability to concentrate – the polyuric phase, where the concentration disorder persists for several months.

Therapy

__ Treatment of acute kidney failure takes place in the nephrology department / ICU. During treatment, it is important to ensure and monitor basic vital functions; fluid balancing with accurate urine collection and hydration status monitoring.

Postrenal ASL: recovery of urine drainage mechanically can take place naturally (urinary catheter, stent) or outside of natural pathways (percutaneous epicystostomy, puncture nephrostomy); then remove your own obstacle at the appropriate time.

Prerenal ASL: restoration of renal perfusion pressure → mean arterial pressure (MAP) 75–80 mm Hg: replenishment of circulating volume in true hypovolemia according to the nature of losses (electrolyte solutions , plasma, blood), improvement of the effective plasma volume in false hypovolemia (plasma expanders, albumin, plasma or blood); MAP < 70 mm Hg: volume adjustment + vasopressor drugs.

Other cases + renal ASL: treatment according to the cause.

Restoration of diuresis in oligoanuria:

• ensuring normovolemia – furosemide in a maximum dose of up to 500 mg i.v. within 30 min,
• 20% mannitol 100–250 ml for crush syndrome + myoglobinuria,
• continuous administration of dopamine at 1.5–2.5 μg/kg/min → vasodilation in the kidneys.

Hyperkalemia: restriction of potassium intake → in case of acute threat:

• acute hemodialysis (most effective),
• 10% calcium gluconicum 10–30 ml i.v. / NaCl 10–30 ml i.v. (inhibition of membrane effect K),
• 40% Glc 250 ml + 24 IU Ins / 8.4% NaHCO₃> 100 ml in 30 min infusion (support of K utilization in the cell),
• ion exchangers Resonium A / Calcium Resonium 1–2 scoops after 2–4 p.o. with lactulose / in a rectal enema.

Hypokalemia (threatened in the polyuric phase of ASL, the onset of anabolism and adjustment MAC): K supplementation (potassium chloride).

Therapeutic nutrition: daily energy intake 160–200 kJ/kg; proteins 0.8–1.2 g/kg, carbohydrates 6–8 g/kg, fats up to 1 g/kg.

Renal function is replaced by extracorporeal purification methods, including intermittent hemodialysis + hemodiafiltration / continuous hemofiltration + hemodiafiltration).

Links

External Sources

Template:Kamera[[1](https://youtube.com/watch?v=VGgKw5f1vR4?&t=705) Acute Tubular Necrosis] – YouTube video

Template:Kamera[[2](https://youtube.com/watch?v=jcXRLh-1gHQ?&t=533) ATN Phases] – YouTube video

Related Articles

• Acute renal failure • Acute renal failure (pediatrics)
• Treatment of acute renal failure
• Chronic kidney disease