Acute Renal Failure

Acute Renal Failure

A syndrome characterized by a sudden usually reversible reduction of GFR manifested by a rapidly progressing azotemia (i.e. an increase in BUN or serum creatinine). A reduction in urine output manifested as oliguria or anuria can also be seen.

Causes of Azotemia with normal renal perfusion:

Exogenous protein loads (diet, hyperalimentation)
Endogenous protein loads (GI bleeding, hypercatabolism)
Rhabdomyolysis – muscle necrosis, release creatinine

Categories of ARF (detailed below):

Pre-renal azotemia (resulting from renal hypoperfusion – 40% of all cases)
Post-renal azotemia (obstruction of urinary tract – 5-10% of all cases)
ARF due to intrinsic renal disease: Acute tubular necrosis (75% of all cases due to intrinsic renal disease), acute glomerulonephritis, renal vasculitis, and acute interstitial nephritis are examples.

1. Pre-Renal (hypoperfusion) ARF

Cause – hypoperfusion of kidney

ECV depletion (hemorrhage, GI losses (vomiting, diarrhea), diuretics)
Reduction in "effective" circulating plasma volume (CHF, cirrhosis, nephrotic syndrome)
Hypotension (cardiogenic, septic, neurogenic shock)

Pathophysiology

reduction in extracellular or "effective" volume Þ Ý sympathetic and Ý RAA Þ ß ß RBF and ß GFR Þ Ý FF

Nonosmotic stimulation of ADH Þ Ý Na⁺ water reabsorption. Urea follows water reabsorption Þ Ý BUN, azotemia

Diagnosis

Physical Exam

Look for signs ECV depletion (orthostatic BP and HR, ß skin turgor, dry mucous membranes)

Look for signs decreased "effective" volume (CHF, cirrhoisis, nephrotic syndrome)

Edema

Invasive techniques: Central Venous Pressure, Pulmonary Capillary Wedge Pressure

Laboratory studies

Blood: Ý BUN and creatinine; BUN/creatinine ratio > 10/1

Urinary sediment: normal

Other Urinary Indices: Urine Na < 20mEq/L; Fractional excretion of Na <1%; Urine Osm >500mosm/L; U/P creatinine >40;

Treatment: If ECV depletion treat with volume replacement. If ß effective volume treat underlying disorder.

2. Post-renal (obstruction) ARF

Cause – obstruction; can occur in ureters, bladder neck, or urethra. Sources include: tones, blood clots, bladder neck, or urethra. Extrinsic sources can be retroperitoneal tumors and retroperitoneal fibrosis. In general, unilateral ureteral obstruction does not cause ARF (or Ý BUN) as the contralateral kidney can compensate. Bilateral ureteral obstruction is uncommon. Prostatic hypertrophy is the most common cause of post-renal ARF.

Pathophysiology: Mechanical obstruction Þ Ý renal tubular pressure and totally negates hydraulic pressure at the level of the glomerulus. Recent studies have shown that in renal obstruction greater than 6 hours, vasoconstrictor substances are formed which ß GFR and ß RBF.

Diagnosis: cathertize bladder to measure post-void residual, renal ultrasound, intravenous pyelogram or retrograde pyelography.

Treatment: removal of stone, catherterize bladder, surgically remove obstruction. The longer the obstruction is present, the more damage to renal function (7 days – 75% return of function; 30 days – 20% return of function).

3. ARF due to Intrinsic Renal Disease

Cause – disease processes that effect one of the four anatomic compartments of the kidney:

Glomeruli - acute glomerulonephritis (AGN)

Blood vessels – vascular disease (malignant HTN, vasculitis, renal arterial or venous thrombosis)

Interstiitum - acute allergic, interstitial nephritis (AIN)

Tubules - acute tubular necrosis (ATN)

Acute Tubular Necrosis

Causes

Ischemic: hypotension, endotoxemia

Nephrotoxic: radiocontrast agents, drugs (especially aminoglycosides), heavy metals (Pb, Au, Hg, Pt, Ur), pigment release (hemoglobinuria, myoglobinuria), many others.

Ischemic injury, nephrotoxic injury Þ cellular damage (cell swelling, Ca overload, mitochondrial dysfunction) Þ mechanisms of hypoperfusion Þ ß GFR

Pathophysiology (Three dominant theories)

(1) Backleak Theory

Damaged tubular epithelium and basement membrane leads to leakage of water and electrolytes into the interstitium and decreases GFR

(2) Tubular Obstruction Theory

Casts lodge in the lumen Þ Ý intratubular pressure Þ ß GFR

(3) Vascular-Glomerular Theories

Constrict afferent Þ ß blood flow to glomerulus Þ ß glomerular filtration pressure Þ ß GFR

Dilate efferent Þ ß glomerular filtration pressure Þ ß GFR

ß glomerular permeability (K_f) Þ ß GFR, but glomerular filtration rate and blood flow are kept normal

In summary: shows the contribution of all three theories to ß ß GFR: Vascular-Glomerular theory (Ý resistance of afferent arterioles); Tubular obstructive theory (Intratubular Obstruction); Backleak theory (Back Leak of Tubular Fluid). ß ß GFR Þ ß flow in renal tubules Þ Oliguria

Cellular effects in ischemic ATN – Both Hypoperfusion and Reperfusion Kills the Cells

Hypoperfusion Þ ß O₂ supply, ß ATP, degradation of adenine nucleotides, Ý hypoxanthine, Ý xanthine oxidase, Ý conversion of hypoxanthine to xanthine with loss of purines to generate ATP Þ cell death

Reperfusion Þ generation of reactive oxygen species, Ý lipid peroxidation, Ý intracellular Ca²⁺, phospholipase activation with further cell membrane dysfunction, Ý Ca²⁺ in mitochondria Þ cell death

Diagnosis of ATN

high level of suspicion in appropriate setting

exclude pre and post renal ARF

urine sediment: muddy brown granular casts; Ý renotubular cells – either free or in casts

Urinary indices:

	Pre-renal ARF	ATN
Urine Na	< 20 mEq/L	> 40 mEq/L
Urine Osm	> 500 mOsm/L	< 400 mOsm/L
U/P creatinine	> 40	< 20
FeNa*	< 1%	> 1%

* Fractional excretion of Na

Prevention

prompt treatment of hypotension including fluid resuscitation
judicious use of nephrotoxic drugs
other approaches: mannitol and other diuretics, vasodilators, Ca²⁺channel blockers, oxygen radical scavengers, administration of ATP

Treatment

Treatment for patients with ATN is supportive, anticipating spontaneous recovery of renal function.
Fluid management: In general administer fluids equal to measured urine losses + 500 mL/day for insensible losses. Na⁺ should be restricted to measured losses or approximately 100 mEq/day. Potassium intake should be minimized.
Acid-base: maintain bicarb at 15, prevent hyponatremia, reduce hyperphosphatemia with aluminum antacids
Calories: Approximately 20 kcal/kg/day, restricted protein to less than 40 grams, emphasizing glucose, fats and essential amino acids.
Drugs: Adjust the dose of all drugs excreted by the kidney (e.g. digitalis, aminoglycosides).
Dialysis: Hemo- or peritoneal dialysis should be initiated to prevent or treat complications of uremia.

Prognosis

Mortality in ARF increases with age, surgical intervention, sepsis, or extensive trauma. Mean mortality rate is 50%. Oliguric patients have a 15-25% higher mortality rate than nonoliguric patients.
Causes of death in ARF include infection and complications of the patients underlying illness.
Recovery of virtually normal renal function can occur and persist for as long as one month. Recovery of GFR should exceed 75% of original function. Subtle defects of tubular function such as mild concentrating defect may be evident many years after an episode of ATN.