Acute renal failure - Pathogenesis, Course and Treatment
Acute renal failure is now known as Acute Kidney Injury, so we shall refer to it as Acute Kidney Injury (AKI) from this point on. We define AKI as a functional or structural abnormality that manifests with one of the following:
- Increased serum creatinine (increase >0.3mg/dL) within 48 hours³
- 1.5 times baseline within creatinine increase within 7 days
- Urine volume <0.5mL/kg/hour for 6 hours (sudden onset oliguria)
There are three stages of AKI
- Stage 1
- Serum creatinine: 1.5-1.9x baseline OR increase >0.3mg/dL
- Urine output: <0.5mL/kg/hr for 6-12 hours
- Stage 2
- Serum creatinine: 2-2.9x baseline
- Urine output: <0.5mL/kg/hr for >12hrs
- Stage 3
- Serum creatinine: 3x baseline OR increase to ≥4mg/dL OR in px <18yrs, decrease in eGFR to <35mL/min per 1.73m
- Urine output: <0.3mL/kg/hr for ≥24hrs OR Anuria for >12 hrs
We can classify AKI into three pathophysical mechanisms:
- Prerenal (60%)
- Intrinsic (30%)
- Postrenal (10%)
We will address the causes, presentation and treatments of each one.
Prerenal AKI
Fundamentally this is caused by hypoperfusion of the kidney, which can be caused by total or intravascular fluid loss (e.g. dehydration or hemorrhage). Prerenal azotemia is divided into volume responsive and nonresponsive forms, depending on if eGFR improves with hydration. For instance, heart failure would be non responsive to hydration, but would respond to beta blockers for instance, this would be non-responsive type. Prerenal AKI is generally reversible, and GFR is maintained in the early stages, however without correction after a number of hours, ischemia can lead to irreversible damage. Examples of what can cause prerenal AKI are:
- Intrarenal vasoconstriction (often from drugs such as antihypertensives, cyclosporins, diuretics, laxatives, NSAIDs, tacrolimus, vasoconstrictors)
- Systemic vasodilation (a result of sepsis or neurogenic shock)
³ Serum creatinine reference is 0.6-1.2 mg/dL
- Volume depletion (overuse of diuretics, vomiting, diarrhea, burns, sweating, blood loss)
Common additional findings to changes in lab results and urine output include vomiting, diarrhea and poor oral intake. It is also important to note that drugs such as NSAIDs, ACEi and ARBs can cause prerenal azotemia. Physical examination may show tachycardia, systemic or orthostatic hypotension and dry mucous membranes.
Intrarenal AKI
Intrarenal AKI is classified based on the primary histological site, the types, with their etiologies, are listed below⁴:
- Tubular (aka acute tubular necrosis, occurs commonly in setting of ischemia or toxins)
- Prolonged hypotension, nephrotoxins such as acyclovir, aminoglycosides, amphotericin, cisplatin, cyclosporin, NSAIDs, mannitol
- Interstitial