Professional Documents
Culture Documents
Acute Kidney Injury1
Acute Kidney Injury1
Clinical manifestation of urinary tract obstruction depend on the location of the obstruction
and time course within which it develops. In general, slowly developing obstructions are
asymptomatic while acute obstruction exhibits symptoms of pain, oliguria/anuria.
Prostatic hypertrophy symptoms such as urgency, frequency, hesitancy may herald
obstructive uropathy (BPH)
Diagnosis
History: - may have obstructive urinary symptoms, hematuria, and flank or suprapubic pain
depending on site of obstruction.
Physical exam: - may have palpable bladder as a suprapubic mass if obstruction is to the
bladder outlet
Laboratory:Elevated BUN/Creatinine
Urinalysis often unremarkable
Hematuria may be present when obstruction is due to stones, cancer
Imaging
Ultrasound is a quick and useful tool that will allow confirmation of the diagnosis of
obstruction.
Dilation of the renal pelvis (hydronephrosis) and ureter (hydroureter) may be seen.
Cystoscopy useful for evaluating bladder and prostate
CT and MRI can identify tumors, stones, adenopathy
Intrinsic AKI
AKI due to renal parenchymal disease
Acute tubular injury
- Ischemic (most common) due to prolonged pre renal state
- Nephrotoxic - Aminoglycosides, Amphotericin, NSAIDs, iodinated contrast, pigment
induced (hemoglobinuria, myoglobinuira)
Glomerulonephritis
Tubulointerstitial nephritis
Vascular vasculitis, thrombotic microangiopathy, renal artery stenosis/thrombosis, cholesterol
emboli
Acute tubular necrosis (ATN)
Acute tubular injury (ATI) is a better term because not all tubules are necrotic; apoptosis and
sub lethal injury are a major component of ATI.
ATI can be
- Ischemic - most common cause of ATI
Prolonged untreated pre renal state ischemic ATI
- Nephrotoxic e.g. Aminoglycoside , Amphotericin, Intravenous contrast , Rhabdomyolysis
Ischemic ATI
Several mechanisms are responsible for tubular injury following ischemia.
- Hemodynamic factors vasoconstriction, endothelial cell injury
- Intra renal inflammation
The renal outer medulla contains tubular segments that have high ongoing energy demand for
sodium transport.
- The third segment (S3) of the proximal tubule
- The medullary thick ascending limb (mTAL)
The combination of high energy needs for transport and the insufficient oxygen supply lead to
tubular cell injury and death of the tubular cells comprising both segments. This tubular cell
injury can persist long after the injury that precipitated the AKI has resolved.
Although the tubule is injured in ATI (not the glomerulus), the hallmark feature of ATI is
reduction in GFR. Mechanism of reduced GFR in tubular injury include
Tubuloglomerular feedback (TGF):- tubular damage results impaired proximal sodium
reabsorption which activates the TGF mechanisms leading to increased afferent vascular
resistance and a concomitant reduction in GFR. Adenosine, a potent renal vasoconstrictor is
thought to be the main mediator of TGF.
Fate of ATI
In most cases, many tubular cells remain viable or are sublethally injured and are able to recover
functionally and structurally. It may take several days or weeks for full recovery to occur. Figure
below shows phases of ischemic ATI.
Phases of ischemic ATI
Treatment: - There is no proven treatment that will reverse ischemic ATI. Therapy is directed at
preventing further injury and allowing recovery to occur. If patients are volume depleted, restore
volume by administering IV fluids, remove offending agents e.g. NSAIDs.
Complications of ATI e.g. Volume overload may require therapy with diuretics, however the
injured tubules may not respond appropriately. Dialysis may be needed for management of
electrolyte abnormalities (e.g. hyperkalemia) and fluid overload. Dialysis is usually temporary
until tubules recover (as opposed to dialysis in advanced CKD where it is either lifelong or as a
bridge to kidney transplantation).
Sepsis and ATI
Sepsis is characterized by vasodilation, decrease in systemic blood pressure (septic shock) and
impaired renal perfusion. These hemodynamic effects contribute to AKI. In addition, sepsis
activates inflammatory cytokines and promotes microvascular injury. Treatment involves
management of sepsis (antibiotics) and hemodynamic support with intravenous fluids and
vasopressors as needed.
Prolonged muscle ischemia from muscle compression e.g. alcohol abuses who fall and do
not move for prolonged periods
Illicit drug use cocaine
Tonic-clonic seizures
Severe electrolyte disturbances e.g. hypokalemia hypophosphatemia
Medication toxicity HMG CoA reductase inhibitors
Clinical features
- Disproportionate increase in serum creatinine, potassium, phosphorous and uric acid
relative to the degree of AKI (since there are released from injured muscle cells)
- Reddish brown urine
- FeNa < 1%
- Positive urinary dipstick for heme coupled with absence of RBCs on urine microscopy
- Increased muscle enzymes in the serum, Creatinine kinase
Treatment
- Aggressive hydration to correct volume contraction, increase renal perfusion and remove
tubular debris
- Alkalanization of urine by administering alkaline IV fluids (bicarbonate instead of saline)
to maintain urinary PH > 6.5 since tubular toxicity of myoglobin is reduced in alkaline
urine
- Correction of electrolyte abnormalities
Intravascular hemolysis with hemoglobinuria can cause AKI due to heme pigment mediated
injury to the renal tubules. Similar to myoglobin induced renal injury, urine dipstick tests +ve for
heme but no RBCs seen on microscopy.
Hepatorenal syndrome
An otherwise unexplained and progressive decline in renal function in a patient with advanced
hepatic disease.
In hepatic cirrhosis, marked splanchnic and systemic vasodilation leads intense intra renal
vasoconstriction.
Patients are typically oliguric and not responsive to fluid resuscitation although the main
underlying pathogenesis is due to depletion of effective circulating volume.
The kidneys are structurally normal and function can be restored if the patient received liver
transplantation.
Tumor lysis syndrome and AKI
Most commonly seen following treatment of hematologic malignancies of high cellular burden
e.g. Lymphoma and leukemia.
Rapid release of intracellular contents of tumor cells into the systemic circulation
Hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia.
AKI is primarily due to acute obstruction of urine flow by precipitated uric acid crystals within
the renal tubules
Treatment: - Aggressive hydration, uric acid lowering (allopurinol, rasburicase)
Management of AKI
Depends on the cause but generally supportive.
Remove nephrotoxic agents.
Restore hemodynamics.
Indications of dialysis in patients with AKI include
- Hyperkalemia
- Pulmonary edema
- Pericarditis
- Severe metabolic acidosis
- CNS symptoms confusion, lethargy, seizures, coma